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Basic Cascades and Messenger Pathways
N/A
258
Biology
Undergraduate 4
09/27/2014

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Cards

Term
Specific Binding
Definition
This occurs when a certain ligand can bind only to specific receptors that accept it. The curve for this will plateau at some point because the binding is saturable, or all the ligands will become occupied.
Term
Non-Specific Binding
Definition
Non-specific binding occurs when there is not a specific ligand and matching receptor that must accept it. Non-specific finding curves will be linear because they will never be saturable
Term
What is the Bmax?
Definition
This is the point at which all receptors for the ligand are occupied, and the binding is saturated
Term
What is the Kd?
Definition

This is the point at which 50% of the receptors are occupied.

 

It can be interpreted however as how well the affinity is of the ligand. A lower Kd represents a higher affinity of the ligand, because it takes less drug to cause receptor binding.

Term
What is a competition curve?
Definition
It represents the drugs ability to compete with other ligands for a receptor. These graphs contain the Ki (next card).
Term

What is the Ki?

Definition

The Ki is found by adding a competitive drug to already saturated receptors/ligands. When half of the receptors have had their ligand replaced with the new competitive drug, you have reached the Ki.

 

Interpretation: the lower the Ki, the more potent/competitive the drug

Term
What is the efficacy of a drug?
Definition
Efficacy refers to the maximum amount of biological effect a drug has on a person. The drug with a higher/stronger maximum effect will have a higher efficacy.
Term
What is the potency of a drug? How does it related to the Kd?
Definition

Potency refers to the dose needed for a drug to have an effect. For example, if one drug requires a smaller amount to have an effect than a competeting drug, it will be more potent.

 

The drug with a lower Kd will have a higher potency because it will take less of the drug to bind to 50% of the receptors, making it much likely to bind. 

Term
What happens when you add a more potent drug with lower efficacy to an already bound and saturated less potent drug with higher efficacy?
Definition
It will decrease the effect even if the previously administered drug is at full efficacy. This is because the more potent drug will kick off the less potent drug that is already bound to the receptors, allowing it to produce its effect.
Term
What is an agonist? Partial agonist?
Definition
An agonist is a drug that when bound to a receptor, fully activates it. A parital agonist will only partially activate a receptor.
Term
What is an antagonist?
Definition
Antagonists do not do anything to the receptor! They simply occupy a receptor so another ligand cannot. In other words, they are inert.
Term
What is an inverse agonist?
Definition
An inverse agonist cause a receptor to do the exact opposite of what it is meant to do.
Term
What are does response curves? How can they be interpreted to reveal the efficacy and potency of a drug?
Definition

Dose response curves graph the amount desired effect of the drug vs. the concentration of the drug administered.

 

A DRC shifted to the left represents higher potency because less of the drug was used to cause the desired effect. A higher dose response curve represents a higher efficacy, because it has a higher overall effect.

Term
How are most DRC's shaped? What is the therapeutic window?
Definition

Most DRCs are an inverted U- at the extremes, the drug has no/starts to lose effect. In the middle, the effect is the highest.

 

A therapeutic window is the range in which a drug can be effective without being dangerous (i.e., when a drug starts producing desired effects to the does at which it is starts to become dangerous). A larger therapeutic window represents a safer drug. 

Term
What are pharmacodynamics?
Definition
The processes of how a drug binds to its target, affects the target, and the physiological response that it causes overall.
Term
What are Scatchard plots?
Definition
They graph the ratio of bound to free ligands against the total bound ligands. They can be used to calculate the Kd and the Bmax (the maximum amount of ligands that can bind to receptors). 1/Kd is the slope, while the x-intercept will represent Bmax.
Term
What are projection neurons?
Definition
Their axons go outside of the CNS and project to tissues throughout the body.
Term
What are interneurons?
Definition
Their axons stay within the nervous system and project to other neurons.
Term
What kinds of structural proteins are present in neurons?
Definition
Actin filaments, microtubules (associated with MAP2 proteins), and intermediate neural filaments.
Term
What in the post-synaptic membrane makes them look dark in images?
Definition
The high concentration of receptor molecules located there.
Term
What dendritic spines? What is their purpose? What makes them so important?
Definition

They are tiny actin filaments coming off the dendrite that reduce space inbetween dentrites and axons, making them close enough to have an actual physical connection.

 

They are so important because they are only part of the adult brain the remains plastic through your lifetime. Their ability to be constantly changing and increasing/decreasing their number makes it possible for us to create more/less synapses and create more/less connections.

Term
What is the a resting potential? mV? Polarization state?
Definition
The resting potential represents the charge of a neural membrane when it is inactive. The membrane is hyperpolarized in this state and rests at -70 mV.
Term
What is an action potential?
Definition
The all-or-nothing event that occurs when a membrane is completely depolarized and a signal is sent down its axon.
Term
What are the concentration gradients of Na and K when a membrane is at rest? What are the charges around the cell?
Definition
There is more sodium on the outside of the cell and more potassium on the inside of the cell. Overall, the charge inside the cell is negative, while the charge outside the cell is positive.
Term
What happens when a membrane is depolarized?
Definition
Voltage-gated Na ion channels open (due to the charge flowing down the membrane) and sodium rushes out, depolarizing the membrane and maintaining the electrical signal. In return, K channels open letting potassium in, repolarizing the membrane.
Term
How is resting potential restored/maintained?
Definition
ATP-dependent ion pumps pump a constant ratio of 3Na ions out and 2K ions in, maintaining the negative charge inside the cell (more + ions out than in).
Term
A cell membrane is a resistor AND a capacitor. What do each of these mean?
Definition
  • Resistance refers to the ease at which ions can cross the membrane, which is dependent on the amount of ion channels contained in the membrane.
  • Capacitance refers to the ability of the membrane to store a charge, which is dependent upon physical membrane properties (e.g., area, thickness, etc.).
Term
What's the most important physcial property of a membrane that affects both resistance and capacitance?
Definition
The myelin sheath, which contains the nodes of Ranvier. This sheath is what speeds of the electrical signals that travel down the membrane.
Term
What is temporal summation?
Definition
This refers to the triggering of an action potential on a dendrite. Regardless of where they are located, if multiple neurons are firing upon another one but in slow succession, they will not cause it to depolarize. If, however, they beging to fire very close together in timethey will cause the target neuron to fire.
Term
What is spatial summation?
Definition
This is the same concept as temporal summation, but in regards to location. In this process. multiple neurons have to be firing at the same time. Whether or not the target neuron fires depends instead on if those neurons are firing very close to each other on the target's membrane or far apart. The closer they are, the more likely the action potential.
Term
What is the general structure of voltage gated-ion channels?
Definition
They are helical bundles that have a voltage sensor in the middle that is positively charged (therefore repelled by the positive charge outside the cell). When the membrane depolarizes, it causes the sensor to move, causing a conformational change in the gate and opening it, allowing ions to rush through.
Term
What are sodium channels responsible for? What can drugs do to affect them?
Definition

They are responsible for the initial depolarization of a membrane, letting Na flow into the cell at will.

 

Certain drugs can sow down the recovery of Na channels from their inactive state, making it harder for them to open. This limits the firing rate of neurons (used to prevent seizures in epilepsy).

Term
What are potassium channels responsible for?
Definition
They are largely responsible for restoring a cell to its resting potential. After the Na channels have opened and depolarized the cell, sending the signal further, K channels open and begin the process of hyperpolarization, back to resting potential.
Term
K channels are delayed rectifiers. What does this mean?
Definition
They undergo delayed activation (after Na channels) and inactivate much more slowly than Na channels. This facilitates repolarization by staying open for longer and allowing more in.
Term
What are calcium channels largely responsible for? When do they open? What are the five types?
Definition

They are responsible for cell signaling. Ca flows into the cell and activates vesicle binding and NT release, leading to second messenger cascades, muscle contraction, etc.

 

They open at about -50 mV, so they require enough Na to flow in before triggering the release of NTs.

 

L, T, P/Q, N, R. P/Q and N are most responsible for NT release.

Term
What are ligand-gated channels?
Definition
These channels are what most NTs bind to (e.g., glutamine, GABA, etc.). Can have all the cascade effects.
Term
What are cyclic nucleotide gated channels?
Definition
These are responsive to cAMP and cGMP
Term
In very basic terms, what are TRP channels?
Definition

Transient receptor potential channels: they are Ca, Na, and Mg permeable. They are extremely important in sensory perception.

 

Chloride channels are included in these; they help damp electrical excitability in cells by keeping the negative charge.

Term
What are astrocytes?
Definition
The support neurons by secreting growth factors such as GDNF. They also play a role in GABA/glutamate uptake in the synapse. They are made of GFAPs, or glial fibrillary acidic protein.
Term
What are microglia?
Definition
They are the resident immune cells of the CNS. They are much like macrophages (white BC that consume cellular debris and bad things); they are inflammatory cells
Term
What are glial cells?
Definition
They are the cell the secrete myelin. They are alos oligodendroctyes, which are much like the myelin sheath in that they insulate a neuron. They also make Schwann Cells in the PNS
Term
What are the layers of the BBB surrounding a capillary?
Definition
There is the usualy endothelial layer surround the capillary. However, instead of the usual fenestrations that allows free diffusion through the capillary, there are tight junctions that close these off. Surrounding this, there are pericytes, another layer, making it harder for molecules to escape. Finally, there is a final layer of astrocytes, further sealing the capillary off.
Term
What defense is contained in the endothelial layer in the BBB to help prevent the escape of molecules?
Definition
There are a ton of transport proteins that have the ability to pump anything that gets out of the capillary back into the lumen.
Term
There are multiple strategies to getting drugs across the BBB. What are prodrugs?
Definition
Because drugs are usualy polar, they cannot cross membranes, but they are too large to fit through tight junctions. Attaching the drug to a prodrug that is lipophilic will make it possible to get through lipid bilayers.
Term
There are multiple strategies to getting drugs across the BBB. How can transporter molecules be used to get into the brain?
Definition

Linking the drug to a molecule that has the ability to bind to and open a transporter molecule can get it through.

 

Ex: TfR receptors and transferum- transferum binds to iron and gets it into the brain through the TfR receptor. Linking a drug to this can get it into the brain with the iron.

Term
Compare readily available to reserve vesicles.
Definition
Readily available vesicles are very close to membrane to allow quick binding in response to Ca release. Reserve vesicles are further back from the membrane and are used if the initial NT supply is depleted.
Term
What does the "post synaptic density contain?"
Definition
They contain not only the high concentration of receptors, but scaffolding proteins that help the receptors reach and bind to the NTs in the cleft.
Term
What causes vesicles to bind to the membrane?
Definition
The depolarization of the cell causes Ca channels to open, which in turn cause vesicles to bind to the membrane.
Term
What is the synaptic fusion complex?
Definition
The set of SNARE proteins that help the vesicles bind and fuse with the membrane.
Term
What are the SNARE proteins and how do they work?
Definition
Synaptobrevin is attached to the membrane of the vesicle. Syntaxin and SNAP25 are located on the membrane of the neuron. When the vesicles approaches the membrane, the SNARE proteins "zip" together and force the vescile to fuse with the membrane, allowing the release of NTs
Term
Compare endocytosis to exocytosis in the cleft.
Definition
Exocytosis refers to the release of NTs, while endocytosis refers to the reuptake of NTs
Term
Where is acetylcholine used in the body? What are its specific receptors?
Definition
It is used in neuromuscular junctions (NMJ). It binds to nicotinic receptors.
Term
What are monoamines? What are the three main subgroups?
Definition
NTs that contain only one amine group. These are catecholamines, indoleamines, and imidazoleamines.
Term
What three major NTs are catecholamines?
Definition
  1. Dopamine
  2. Norepinephrine
  3. Epinephrine
Term
Catecholamines are all made from the same starting material. What is this compound?
Definition
Tyrosine
Term
What is series/order in which the catecholamines are made?
Definition
Tyrosine --> Dopamine --> Norepinephrine --> Epinephrine
Term
What enzymes turn tyrosine to dopamine, and what is the intermediate?
Definition
Tyrosine hydroxlyase turns tyrosine into DOPA. DOPA is then turned into dopamine by L-aromatic amino acid decarboxylase.
Term
How is dopamine turned into norepinephrine?
Definition
β-hydoxylase creates norepinephrine from previously exisiting dopamine compounds.
Term
Finally, in the same fashion, what enzyme turns norepinephrine into epinephrine?
Definition
Transferase
Term
What major NT is in the indoleamine subclass?
Definition
Serotonin, or 5-HT
Term
What is the sequence to create serotonin?
Definition
Tryptophan is turned into 5-hydroxytrytophan by tryptophan-5-hydroxylase5-hydroxytrytophan is then turned into serotonin by t-amino acid decarboxylase.
Term
What is the major NT in the imidazoleamine sublcass?
Definition
Histamines
Term
What are histamines made from?
Definition
Histidine is turned into histamine by histadine decarboxylase.
Term
What do we model many of our drugs after? Why can't we just administer peptides?
Definition

Endogenous peptides that already exist in the body. However, we come up with creative ways to administer them because most peptides get chewed up in the gut before even getting into the blood stream.

 

All endogenous peptide sequences have active sequences that can be cleaved out and identified, along with different properties (e.g., hydrophobic, polar, acidic, basic, etc.).

Term
Are there endogenous cannabanoids in our bodies? Why are their receptors important?
Definition
Yes there are. The CBI receptors are important becase they dampen excitability on those neurons.
Term
What are ionotropic receptors? How many different kinds are there? Are they fast or slow?
Definition
These are ligand-gated ion channels, and results in fast synaptic transmission. When NTs bind to these, they open them up, allowing the flow of ions into a neuron (Na and Ca). There are 14 kinds of these receptors.
Term
What are metabotropic receptors? How fast are they?
Definition
These are g-protein coupled receptors. They result in slow synaptic transmission. When NTs bind to these, they activate the g-proteins inside of the membrane, which can lead to thousands of different responses, depending upon which receptor is being activated.
Term
What is the quantal neurotransmitter release theory?
Definition
This theory was created due to the observation of random and accidental NT releases ("leakiness") that caused small amplitude responses in the most-synaptic neuron. What this led to is the theory that NTs are released in quantal amounts/events into the cleft from the nerve terminal, and confirmed that vesicles bind and release NTs into the cleft in response to signals.
Term
After NTs are released into the cleft, what are their two "fates" aftwards?
Definition
  1. They can be broken down by an enzyme, then transported back into the neuron in that state. Ex: aceytlcholine is borken down into choline by acetylcholineasterase.
  2. NT Transporters reuptake the NT back into the cell to be repackaged and resued (e.g., serotonin).
Term
What NT Transporter is in charge of the reuptake of monoamines?
Definition
The VMAT2 transporter, which can take monoamines back into the presynaptic cell.
Term
What NT transporter is responsible for reuptake of choline in the presyaptic cell?
Definition
VAChT
Term
What do reuptake inhibitors do (e.g., SSRIs)?
Definition
They block the NT transporters on the pre-synaptic cell (such as VMAT2), causing the NTs to remain in the cleft longer than normal and prolonging their effect.
Term
How is actylcholine made?
Definition
Acetyl CoA and choline are combined by choline acetyl-transferase (a synthetic enzyme) into acetylcholine.
Term
What is glutamine? What is it synthesized into/broken down into? What two enzymes are responsible for this?
Definition
The main excitatory NT in our bodies. Glutamate is made into glutamine by glutamine synthetase. It can then be broken back down into glutamate again by glutaminase.
Term
What are the five main steps of vesicle fusion and transmission release? (Name the five steps here, a card for each one follows)
Definition
  1. Docking
  2. Priming
  3. Fusion
  4. Endocytosis
  5. Recycling
Term
What is the docking stage?
Definition
The vesicles moves to the membrane becomes loosely associated with it, but not yet fused to it.
Term
What is the priming stage?
Definition
The vesicle is made ready for fusion and release of NTs by preparing the SNARE proteins. Only primed vesicles can release NTs.
Term
What is the fusion stage?
Definition
When a Ca influx causes a vesicle, through v-SNARES (on later card), to bind fuse with the membrane and release NTs.
Term
What is the endocytosis stage?
Definition
The stage during which the vesicle is pinched off of the membrane by dynamin (a pinchase) and transferred back into the neuron (more detailed card later).
Term
What is they recycling stage?
Definition
The vesicle can be reloaded with NTs and used again later if needed.
Term
What's the difference between a v-SNARE and a t-SNARE?How do these SNARE proteins dock a vesicle to the membrane?
Definition

v-SNARES are vesicular SNARES, and t-SNARES are target SNARES.

 

The v-SNARE protein is called synaptobrevin. After the vesicle is primed, it can interact with the t-SNARES on the membrane, SNAP-25 and syntaxin. They zip together and pull the vesicle into the membrane, fusing it and releasing NTs.

Term
How are the SNARE proteins broken apart so the vesicle can be removed from the membrane?
Definition
The use of NSF and SNAP (a completely different protein than SNAP-25). SNAP is an adaptor protein that binds to the SNARE complex. NSF can then bind to SNAP and use ATP  to break apart the entire complex.
Term
How does botox affect SNARES?
Definition
Botox cleaves the v-SNARES, so the vesicles cannot bind to the membrane. This keeps them from releasing NTs (acetylcholine) and the muscles from tightening.
Term
What's the name of the Black Widow toxin disrupts vesicle fusion? (Not sure if this is important, but he mentioned it in class one day, specifically that we would know it if we read the book)
Definition
α-latrotoxin
Term
How is a vesicle pinched from the membrane? What proteins are used?
Definition
Two adaptor proteins, the AP-2 complex and synaptotagmin bind to the vesicle membrane. These all clatherin proteins to bind and form a clatherin coat. Two adaptor proteins, synaptojanin and amphiphysin to bind, which dynamin binds to. Dynamin is a pinchase/GTPase that uses GTP hydrolysis to pinch the vesicle away from the membrane.
Term
What is the synapsin tethering protein for?
Definition
It binds to actin and tether vesicles to the cytoskeleton. This is what helps the neuron maintain different pools of vesicles.
Term
What is the synaptotagmin sensor protein for?
Definition
It is a calcium sensor. When there is a Ca influx, the Ca binds to it and that leads to vesicle fusion.
Term
What are the four main types of receptors on/in a post-synaptic neuron that a NTs/ligands can bind to?
Definition
  1. Ionotropic/ligand gated ion channels
  2. Metabotropic/g-protein coupled receptors
  3. Tyrosine kinases
  4. Steroids and steroid receptors inside the membrane (steroids can traverse the membrane)
Term
What (very basically) do g-protein coupled receptors and tyrosine kinases lead to?
Definition
Protein phosphorylation cascades the leads to the generation of 2nd messengers, which activate more protein kinases, and in the end lead to a biological response. Tyrosine kinases usually involve different phosphorylation processes of tyrosine.
Term
What does the Gαs subunit do?
Definition
It is a stimulatory protein that turns on andenylyl cyclase: this converts ATP into the 2nd messenger cAMP (cyclic AMP).
Term
What does the cholera toxin do to the Gαs protein?
Definition
It adds a sugar molecule, forcing it to stay active, promoting excessive production of cAMP.
Term
What proteins are GAPs for the s family?
Definition
RGS proteins
Term
What does the Gαi protein do?
Definition
It is an inhibitory protein that turns off andenylyl cyclase: this stops the creation of cAMP.
Term
What does the pertussis toxin do to the Gαi protein?
Definition
It adds a sugar molecule and inhibits it, still promoting cAMP.
Term
What does the Gαq protein do?
Definition
This protein turns on phospholipase C: this makes two 2nd messengers: IP3 and diethylglycerol.
Term
What are the three subunits of a G-protein? What is their conformation in their inactive state?
Definition
There is an alpha, beta, and gamma subunit. In an inactive state, the three subunits are bound together, and the alpha subunit has GDP bound to it.
Term
What is the general process for all G-proteins when a ligand binds to their receptor?
Definition
The bound ligand causes a conformational change in the receptor, causing alpha to have a higher affinity for GTP. It in turns lets go of the bound GDP and binds a GTP. The binding of GTP causes alpha to dissociate from beta and gamma. The alpha unit can then go activate a separate target protein, which causes further downstream signalling. After this, the alpha unit hydrolyzes the GTP into GDP with the help of RGS. It then binds back to beta and gamma, turning off any target proteins. A receptor can activate thousands of g-proteins in the time that it is activated.
Term
How is a g-protein coupled receptor turned off?
Definition
A receptor kinase can phosphorylate the receptor. This then allows an arrestin protein to bind, which inactivates the receptor by blocking its interaction with g-proteins. The arrestin protein, if needed, can lead to the endocytosis of receptors proteins where they can later be degraded or used again.
Term
What are GEFs?
Definition
GEFs are guanine nucleotide exchange factors that promote the exchnage of a GDP for a GTP on monomeric g-proteins.
Term
What are GAPs?
Definition
GAPs are GTPase-activating proteins and they promote the phosphorylation of GTP to GDP on monomeric g-proteins.
Term
What are monomeric g-proteins?
Definition
They are small molecular weight g-proteins that are often part of signal transduction and protein pathways (e.g., RAS).
Term
What is the Ras protein involved in?
Definition
The MAP-K pathway, which controls cell proliferation. It is mutated in about 70% of human cancers.
Term
What turns ATP into cAMP? What degrades cAMP? What it is degraded into?
Definition
Adenylyl cyclase turns ATP into cAMP. cAMP can be degraded into 5'-AMP by phosphodiesterase.
Term
What is cAMP? What are its jobs (importantly its main one)?
Definition
cAMP is a 2nd messenger. It can bind to certain ion channels, but it's main job is to turn on protein kinase A (PKA), which can go on to activate more protein kinases.
Term
What is cGMP? What are its jobs?
Definition
cGMP (cyclic GMP) is a 2nd messenger. It can gate ion channels, but its main job is to turn on protein kinase g (PKG) which can then go and phosphorylate other kinases.
Term
What is cGMP made from?
Definition
It is made from GTP by guanylyl cyclase by interacting with NO (nitrous oxide); a higher amount of NO in the cell will result in the creation of more cGMP.
Term
How many types of adenylyl cyclase are there?
Definition
8
Term
What one protein beaks down both cAMP/cGMP/cyclic nucleotides?
Definition
Phosphodiesterases; there are 7 families of them, each one has different characterstics and breaks down different nucleotides.
Term
How do Gαq proteins create their 2nd messengers? What are these 2nd messengers?
Definition
Gαq binds with phospholipase C beta, which hydrolyzes lipids to generate 2 second messengers. These 2nd messengers are IP3 and DAG.
Term
What does DAG stand for? What does it do?
Definition
DAG stands for diethylglycerol. It directly activates PKC (protein kinase C).
Term
What does IP3 stand for?
Definition
IP3 is a sugar that goes into the endoplasmic reticulum to an IP3 receptor and binds to it. This opens a channel that lets Ca out of the ER and into the cytosol.
Term
What the IP3 gated receptor channel is opened, what does the Ca that is released do?
Definition

It has two different jobs:

  1. Ca can activate NO synthase, which is used to help make GTP.
  2. Ca can bind to calmodulin. This compound can then activate various CaMPK (Ca/calmodulin protein kinases).
Term
How does PKA affect Ca levels in a post-synaptic cell?
Definition
Activation of PKA can affect Ca channels by increasing the likelihood of Ca flowing into the cell, increasing the firing rate of the neuron.
Term
What receptor can norepinephrine bind to that turn on PKA?
Definition
Norepinephrine can bind to the β1 agonergic receptor, which turns on PKA, and opens up Ca channels, increasing contractions in the heart.
Term
What happens to IP3 after it is used?
Definition
It is recycled. Through a series of phosphorylation reactions, enough phosphates are taken off to create inositol. This inositol can be resued to make PIP2 again.
Term
What is PIP2?
Definition
PIP2 (phosphatidylinositol 4,5 bisphosphate) is the initial lipid that is hydrolized by phospholipase C at the Gαq protein to create DAG and IP3.
Term
How does Li (lithium) interact with IP3 recycling?
Definition
It traps inositol in the 2nd to last step, so it can't reform and create PIP2, the main substrate for DAG and IP3. This is important because it decreases the ability to stimulate neuromal activity. This is the hypothesis as to why it works as a medication for bipolar disorder.
Term
What are the two different isoforms of phospholipase C? How do they differ in function?
Definition

There is phospholipase C-β and phospholipase C-γ. Beta is activated by the Gαq subunit.

Gamma is activated exclusively by receptor tyrosine kinases due to the presence of the SH2 domain.

Term
What are all 2nd messengers derived from?
Definition
Lipids
Term
What is arachnidonic acid used for?
Definition
Enzymes that act on this acid can turn it inot leukotrienes and prostycyclins.
Term
What are the general functions of leukotrienes and prostacyclins? What can help turn the prostacyclins off?
Definition

They can regulate adynylyl cyclase, gunaylyl cyclase, ion channels, protein kinases, and other cellular proteins.

 

Antiinflammatory medicines can turn of cyclooxygenases, stopping their production. However, too much of these is bad.

Term
There are 8 ways to regulate intracellular calcium. List them.
Definition
  1. Voltage gated ion channels (action potentials depolarize these and let Ca in).
  2. Ligand gated ion channels (MMDA receptors open them)
  3. Na/Ca exchanges: Na in, Ca out.
  4. Ca Pumps: use gradient to get Ca out and H in
  5. Ryanodine: lets Ca out
  6. ATP/ADP Pump: Ca in
  7. Ca binding buffer proteins
  8. IP3: binds to IP3 receptor to let Ca in
Term
What's the difference between a kinase and a phosphotase?
Definition
A kinase will put a phosphate on, while a phosphotase will take a phosphate off.
Term
What are the three types of kinases? What can they interact with in a cell?
Definition
Serine-threonine kinasestyrosine kinases, and lipid kinases. The serine-threonine kinase can only phosphorylate serine or threonine chains, which are active in many protein kinases in a cell. Tyrosine kinases have dual specificity, meaning they can phsophorylate any protein or kinase. Lipid kinases phosphorylate lipids.
Term
What are the most common pathways that the serine-threonine kinases interact with?
Definition

The MAP-K and ERK pathways

PKA, PKG, and PKC pathways

Term
Are phosphotases and kinases in balance?
Definition

No, many phosphotases dephosphorylate proteins that PKA/G/C may phosphorylate. Phosphotases are dominate, so to generate a signal you have two options:

You can inhibit the phosphotases, which is extremely difficult.

Or you can activate much more kinases than phosphotases.

Term
What is the structure of PKA?
Definition
It is a dimer. There are two monomers linked by a disulfide bridge. Each monomer is made up of a regulatory and catalytic subunit that are bound together when inactive.
Term
How is PKA activated?
Definition
cAMP binds to the regulatory subunits. This casues them to dissociate from the catalytic subunits so they can go on to bind to and activate other proteins.
Term
What is the structure of PKG? How does it get activated?
Definition
Similar to PKA, it is a dimer bound by a sulfide bridge, with regulatory and catalytic subunits. For PKG, when cGMP (not cAMP) bind to it, it causes not a dissociation but a conformational change, opening up the catalytic subunits to interact with other proteins.
Term
What is the structure of PKC? How is it activated?
Definition
PKC has a pseudosubstrate attached to a chain, ending with a catalytic subunit. Either Ca, PS, or DAG can bind to the pseudosubstrate end, causing a conformational change and opening up the catalytic subunit.
Term
What is an NGF? What do they bind to?
Definition
It is a nerve growth factor. They bind to a specific receptor, Trk-A (a tyrosine kinase).
Term
What is a neutrophin?
Definition
They are primarily responsible for promoting suvival and growth for neurons.
Term
What is the structure of a Trk-A receptor? How does it work?
Definition
It is a dimer with two binding sites on the outside of the membrane. When an NGF binds both binding sites, it causes a conformation change. The dimers move closer to each other, activating transautophosphorylation. This creates multiple phosphotyrosine binding sites on the intracellular parts of the receptor that are recognized by SH2 binding domains.
Term
What are the three important proteins that have SH2 binding domains (the three that are used for the three pathways on the next cards)?
Definition
Grb2, PI-3-K, and PLCgamma all have SH2 binding domains.
Term
Describe the MAP-K pathway. Know how it starts, the order of the proteins, why they like each other, and what the biological response of this pathway is.
Definition
After Trk-A is phosphorylated, Grb2, an adaptor protein with an SH2 domain, binds to the receptor. Sos then binds to Grb2, because sos has an SH3 domain that recognizes the proline rich sequences of the Grb2Sos is a GEF for Ras. Therefore, it turns ras from an inactive GDP bound state to an active GTP bound state. Ras then turns on Raf, a serine-threonin kinaseRaf turns on MEK (a dual specificity kinase) that phosphorylates ERK (a MAP-kinase). Erk goes to the nucleus and directly phosphorylates transcription factors to cause proliferation.
Term
To break it down, simply name the proteins and their order in the RAS/MAP-K pathway, without describing how they interact with each other.
Definition
Grb2 --> Sos --> Ras --> Raf --> MEK --> ERK --> Biological response
Term
Now name name simply what function each protein performs.
Definition
  • Grb2: an adaptor protein with an SH2 domain (enables the binding of Sos)
  • Sos: a GEF for Ras 
  • Ras: a GEF for Raf
  • Raf: a serine-threonin kinase that runs on MEK
  • MEK: a dual specificty kinase that turns on ERK
  • ERK: a MAP kinase that turns on transcription factors
Term
What is the PI-3-K/AKT pathway? How does it function and what does it do?
Definition
It begins with PI-3-K, a protein with an SH2 binding domainPI-3-K through a series of multiple steps activates AKT (the same thing as PKB). AKT goes on and phosphorylates transcription factors, which turn on pro-survival genes.
Term
What is the PLCgamma pathway? What does it do?
Definition
PLCgamma has an SH2 binding domain. PLCgamma cleaves PIP2 to generate IP3 and DAGIP3 causes the release of Ca and DAG activates PKC.
Term
How do proteins "know" who to interact with?
Definition
Certain domains on proteins like to interact with each other, and will only bind to certain other proteins. These are called protein motifs.
Term
What two main domains should we know for the test?
Definition
  1. SH2 Domains: these like to interact with phosphotyrosine binding sites (ex: PLCgamma or Grb2)
  2. SH3 Domains: these like to interact with polyproline rich sequences (ex: sos, the GEF for Raf)
Term
What are the two ways to turn off a g-protein receptor?
Definition
Autoinhibition and the βagonergic receptor kinase, or βARK.
Term
How does autoinhibition work?
Definition
This is the process of PKA actually coming back up to the receptor and phosphorylating it, desensitizing it to g-proteins.
Term
How does the BARK function?
Definition
It is a g-protein coupled receptor kinase. It phosphorylates the receptor which creates binding sites for β-arrestin, which prevents it from coupling to anymore G-proteins and activating them.
Term
What process are the most common proteins found in neurons regulated by?
Definition
Phosphorylation processes that turn them off and on.
Term
What does tyrosinehydroxylase do? What is it regulated by?
Definition
It is a rate limiting enzyem in the synthesis of all catacholamines- it is in charge of the synthesis and degradation of NTs). It is regulated by PKA, PKC, and CaM-KII (they increase its effect)
Term
What is Tau? What regulates it?
Definition
It is a microtubular bundling protein, and it can be phoshporylated by a serine-threonin kinase (CDK-5).
Term
What is synapsin? What is it regulated by?
Definition
It tether vesicles to the actin cytoskeleton (creating the different pools). It is regulated by PKA and CaM-KII.
Term
What enzymme unwinds DNA?
Definition
Helicase
Term
What main enzyme is involved in the creation of RNA?
Definition
RNA Polymerase
Term
What structure is DNA naturally stored as within the cell? Why?
Definition

DNA is stored in tightly wound around proteins called histomes. The single unit of a histome and its surround DNA is called a nucleosome. The entire wound up DNA strand is called chromatid.

 

This structure is the cells natural way to inhibit transcription of genes unless specifically activated by signaling cascades.

Term
What enzyme unwinds DNA to being the transcription process?
Definition
Helicase
Term
What binds to unwound DNA to get it ready for the machinery to bind?
Definition
Transcriptional activator proteins/transcription factors
Term
What proteins and enzyme bind to DNA to begin transcription?
Definition
Basal transcription complex, TFIID, preinitation complex, and the RNA polymeraze bind to the open DNA
Term
What exactly is the job of transcription factors? What is their structure?
Definition
Transcription factors usually bind as dimers to the DNA at a specific motif on the promoter region of the gene. They then recruit chromatin modifer proteins like HATs.
Term
What are HATs? What do they do? Why is this necessary for transcription?
Definition
Histone acetyltransferase. They acetylate the histomes which makes them negative, repelling themselves away from the DNA so it can be unwound.
Term
Opposite of transcription factors, what do inhibitor factors recruit to DNA?
Definition
HDATs, or histome deacetyltransferase. These methylate histomes, making them less positive and more attracted to DNA again, making it harder to unwind.
Term
What are the four states of chromatin, and how do the relate to transcription?
Definition
  1. Active: chromatin is acetylated and unwound, and transcription is ocurring
  2. Permissive: histomes are heaveily acetylated and chromatin is ready for transcription to beging
  3. Repressed: the chromatin is primarily methylated
  4. Inactive: histomes and the DNA itself are methylated, furthest from transcription
Term
What does MeCP2 do to DNA? What happens when there is a mutation to this protein?
Definition
MeCP2 highly methylates DNA, stopping gene transcription. A mutated version of this protein results in genes that should be repressed getting turned on. Can result in Rhett Syndrome
Term
How do our cells manage to make so many different RNA sequences from so few genes?
Definition
Alternative splicing
Term
How does alternative splicing work? Roughly how many gene sequences do we have? And roughly how many proteins can we turn these into?
Definition
The cell takes a primary RNA transcript from a gene region and splices out various regions of the RNA to make different variants. In the end, RNA sequences with even small differences end up creating different proteins. We manage to create 100,000 proteins from only 25,000 genes.
Term
What are mRNAs? What do they do?
Definition
Messenger RNAs. They carry the sequence of amino acid chains from the DNA into the cytoplasm and where it is made into proteins.
Term
What does microRNA do? What three spots can they regulate at?
Definition
They can bind to mRNAs and shut of translation of them, in turn inhibiting the production of proteins. They can regulate transcription, translation, and by phosphorylating proteins after they made.
Term
What three main elements make up transcription factors? What does each do?
Definition
  1. DNA Binding Domain: this is what recognizes the DNA sequence
  2. Protein Dimerization Domain: this connects the transcription factors, creating a dimer
  3. Transcriptional Activation Domain: this can be phosphorylated by certain protein kinases at phosphorylation sites, however the primary job of these is to recruit proteins such as HATs.
Term
What is the TATA do?
Definition
The TATA binding protein (TBT) recognizes the TATA box and binds to it. The TBT then brings in RNA polymerase II (and other proteins).
Term
How is CREB activated? Is it always expressed?
Definition
CREB is always expressed, but needs to be phosphorylated to be activated.
Term
What are immediate proteins?  Give three examples. Where are they located? Are they always expressed?
Definition
Immediate proteins are named so because they act very fast and then are quickly broken down. FOS, JUN, and AP1 are three examples. They are located downstream of CREB and are not expressed until CREB activates them. They then go and act as transcription factors.
Term
What is NFkB? What does it do?
Definition
Term
What is NFΚB? What is it involved in?
Definition
Nuclear Factor kappa B. It is involved in immune response, particularly in inflammatory pathways and cancer. Even more specifically it turns on the transcription factor for microglia ("immune cells of the CNS")
Term
How does NFkB work? What is the specific mechanism and pathway?
Definition
The dimer p50-Rel-A (p50/Rel-A) is bound to IkB (inhibitory kappa Bnormally. When NFkB is activated, the IkK (I kappa b kinase) phosphorylates IkB, causing it to let go of the dimer and become "iniquibitated," which signals it to get eaten up by lysosomes. The heterodimer p50-Rel-A then goes and binds to the kB transcription site.
Term
What are the three pathways that can activate CREB?
Definition
  1. Gq receptors can generate calcium, which can combine with calmodulin to create CaMK, which can phosphorylate CREB
  2. Gs receptors activate AC, which makes cAMP, which activates PKA, which through more steps activates CREB
  3. Tyrosine kinases can go through Ras, Raf, MEK, and ERK (the normal MAP-K pathway), but then instead activate RSK which can activate CREB
Term
What are three specific things that CREB can turn on (three he mentioned in class)?
Definition
  1. kB
  2. FOS
  3. JUN
Term
Why is it useful that CREB has so many different converging pathways?
Definition
It is easier to regulate.
Term
What is a CRE? What is unique about them? Why is this important?
Definition
A cyclic AMP response element. They are strands of the DNA that are palindromes (the exact same backwards as they are fowards). The palindrome is what CREB recognizes and binds to, it is required for transcription. A stronger palindrome means a stronger binding site.
Term
What does CREB actually stand for?
Definition
cAMP response element binding-protein
Term
What are c-Fos and Jun? How do they interact? What do they do?
Definition
c-Fos and Jun are both transcription factors. They are technically two different factors but are most commonly found together as a dimer. As a dimer, they bind to the AP-1 region (another palindrome like CRE), converting cellular signals to gene expression.
Term
What is the difference between c-Fos and FosB isoforms?
Definition
c-Fos is an immediate protein that acts quickly and is then quickly degraded. FosB is a much more stable and long lasting T-factor that does not have as strong of a response, but lasts longer.
Term
What can repeated stimulation do to FosB?
Definition
It can build them up so when they are activated they last even longer.
Term
What is haloperidol?
Definition
It is a dopamine D2 antagonist.
Term
What is common between dopamine and amphetamines?
Definition
They both actiavte the C-Fos, but in different regions.
Term
What is c-Fos related to (what response does it actually cause)?
Definition
It is related to proliferation. In cancer, you often see over expression of c-Fos.
Term
What are three regulatory sites of c-Fos we should know?
Definition
  1. Upstream of TATA, there's a CRE (which binds CREB). CREB activates c-Fos. CREB has to be phosphorylated by either glutamate (or other neuromodulaters) or RSK to be activated.
  2. Further upstream of CRE, there's a serum response element (SRE), which can also activate CREB. SRE needs to be activated (somehow) for c-Fos expression.
  3. Upstream of SREs, there's a group of cytokines (compounds excreted my inflammatory cells), which signal through the tyrosine kinase pathway (however cytokines are not an actual tyrosine kinase, they activate one lower downstream, which then activates STATS).
Term
How can steroids/hormones regulate transcription?
Definition
Steroids can bind to a receptor and be translocated into the nucleus (such as cortisol). Cortisol can activate glucocorticoid receptors, which dimerize GRE, and turn on, repress, or inhibit AP1 transcription.
Term
How is glutamate made?
Definition
Glutamate is synthesized by glutaminase from glutamine.
Term
What compound is glutamate similar to?
Definition
Aspartate. They can even activate many of the same receptors, and can be converted back and forth between one another.
Term
What does glutaminase work?
Definition
It works within the presynaptic cell, making glutamate which gets put directly into vesciles, which can fuse and release the glutamate after receiving an action potential.
Term
What are the two main ways glutamate can get back into the presynaptic cell?
Definition
  1. They can get taken directly back in by EAAC1 receptors as glutamate.
  2. GLAST or GLT-1 receptors on astrocytes take glutamate back up into glial cells. They then turn it into glutamine, which can be put back out and taken up again into the pre-synatpic cell.
Term
Why bother going through the process of turning glutamate back into glutamine within the glial cells?
Definition
Glutamine can traverse the membrane better than glutamate, making it easier to transport.
Term
What is the main effect of glutamate? Can it ever be bad?
Definition
The increase of Ca within a cell, increasing the likelyhood of an action potential. Yes. If it's not cleared from the cleft quickly enough and too much Ca enters the post cell, it can result in excitotoxicity.
Term
How is glutamate involved with ALS?
Definition
ALS patients are unable to use their GLT-1 transporter, so glutamate cannot be taken out of the cleft.
Term
What are the two types of glutamate receptors?
Definition
  1. Ionotropic: glutamate binds directly to a ligand gated channel and ions flow in
  2. Metabotropic: g-proteins
Term
What are the three classes of ionotropic receptors for glutamate? What is similar between them all (in terms of structure and function)?
Definition
  1. AMPA
  2. Kainate
  3. NMDA

They are all cation channels, meaning they pump sodium in and potassium out. They are all also technically tetramers (AMPA isn't fully)

Term
What is structurally different about an AMPA/GluR1-4 ionotropic receptor? Where does glumate bind?
Definition

There are only three transmembrane domains. The fourth, located between T1 and T2, does not go all the way through. This is the Q/R-site. There is also a "flip-flop" region, which is two spliced variants of each subunit.

 

Glutamate binds to the extracellular regions of T1 and T2.

Term
What is the Q/R-site?
Definition
It controls the permeabilit of calcium (how much is able to get through)
Term
What are NMDA receptors more associated with?
Definition
They move mostly calcium and less other cations. They are most often involved in excitotoxicity.
Term
What are AMPAkines?
Definition
These drugs mimic the actions of glutamate, but also slow AMPA receptor deactivation, prolonging a longer boost of excitatory transmission.
Term
What is a good antagonist for NMDA receptors?
Definition
MK801
Term
What is a good antagonist for AMPA receptors?
Definition
NBQX
Term
What is the difference between AMPA and NMDA receptor activation?
Definition
AMPA receptors come on strongly and quickly because they do not need to be highly depolarized. When glutamate binds, they go. But they deactivate very quickly. NMDA receptors come on more slowly and are more weak, but stay on for a longer period of time because they are voltage independent.
Term
Why does this difference exist between AMPA and NMDA receptors?
Definition
NMDA factors need more depolarization before activating because they have a magnesium block (remember they're voltage independent, so its the Mg that needs to be moved, not that the actual receptor needs to be depolarized)
Term
How does the magnesium block work?
Definition
Mg in the extracellular space blocks NMDA receptors from being activated and conducting sodium. The depolarization of a cell kicks Mg out, allowing the NMDA to open.
Term
Why is it harder to activate NMDA then AMPA?
Definition
AMPA can be activated by just a single, leaked glutamate molecule, while NMDA receptors need multiple inputs from the precell (summation) so the membrane can depolarize and move Mg out.
Term
Which of the two receptors is long-term potentiation affiliated with? Why?
Definition
NMDA. Because NMDA receptors stay on for much longer. Along with this, the stronger the input/stimuli, the more signals cells will receive, and the longer/stronger NMDA receptors will stay on for.
Term
Again, what are NMDA receptors mainly responsible for? Can they interact with other cations?
Definition
NMDA receptors mainly move calcium in, but they can also move sodium in. They can allow K to leave, but definitely do not supply the main route for K
Term
The NDMA receptors already have the magnesium block. Along with this, they have another for of regulation. What is it?
Definition
They have a coreceptor, and hence a coagonist. There is a glycine?/D-serine? binding site AND glutamate binding site on the receptor. Both must bind for NMDA receptors to open.
Term
Why are NMDA receptors so regulated?
Definition
Overstimulation kills neurons, and as adults we cannot create new ones, so it's crucial for NMDA receptors to prevent this.
Term
What are three major antagonists of NMDA receptors?
Definition
PCP, ketamine, and MK801
Term
What feedback loop does NMDA have to prevent overstimulation?
Definition
If enough calcium is let into the cell, it will begin to bind with calcineurin. This signals it to go back to the NMDA receptor and dephosphorylate it, shutting it off.
Term
There are three groups of metabotropic glutamate receptors. What g-protein is each associated with?
Definition

Group 1 receptors are coupled to Gq receptors and are primarily located on the post cell.

 

Group 2 and 3 receptors are coupled to Gi and Go, and are found on pre cell terminals

Term
Why have Gi and Go proteins on the precell for glutamate?
Definition
Both shut off adenylyl cylclase, decreasing the amount of NT release; they can also suppress voltage gated Ca channels.
Term
What is the structure like for metabotropic glutamate receptors?
Definition
The have 7 transmembrane pieces
Term
What packages glutamate into vesicles?
Definition
VGluT
Term
How does the activation of the group II and III glutmate receptors stop glutamate release?
Definition
Ca is what causes vesicles to fuse to the membrane and release their contents. When glutamate binds back on the autoreceptors, the reaction is the suppression of voltage gated Ca channels.
Term
What does GluR2 do to AMPA receptors?
Definition
They block the influx of Ca through the channel (not all AMPA have these, but most do)
Term
What is each type of receptors preferred type of scaffolding (each receptor has a strong affinity for a certain type)?
Definition
  • PSD-95: NMDA
  • Stargazin!: AMPA
  • Homer: will bind to all mGluR (metabotrobic) receptors.
Term
Where does each type of scaffolding locate the receptors?
Definition
PSD and Stargazin! will move AMPA and NMDA receptors close to each other. Homer scaffolding brings its receptors away from the center so glutamate has to slightly diffuse before it can reach them
Term
What is long term potentiation? Why does this happen?
Definition
This occurs when a cell is stimulating many times in progression, causing the response to last much longer than it normally would. In vivo, LTP can last for weeks. The NMDA receptors being activated for so long lead to an increase in AMPA on the post cell.
Term
There are five theories to LTP. What is the NMDA-dependent theory (true one)?
Definition
NMDA activation brings in a lot of Ca, which with calmodulin creates CaMKII. CaMKII plays a large role in bring up AMPA receptors to the membrane
Term
What is the NMDA-dependent theory of LTD(the one he doesn't like)?
Definition
NMDA doesn't bring in enough Ca to make CaMKII, only to make Calcinneurin and PP1, which take the AMPA away from the membrane
Term
What is the mGluR-dependent theory of LTD?
Definition
Activation of mGluR1/5 lead to the internalization of AMPA
Term
What is presynaptic theory of LTP?
Definition
Activation of the pre-synpatic Ca channels in addition to the action potential (that's also causing Ca output) leads to way more glutamate getting put out (this is done by the Ca activating adenylyl cyclase, which makes cAMP, which activates PKA, which through other proteins increases glutamate)
Term
What is the theory of presynaptic LTD?
Definition
Heteroinhibitory receptors on the presynaptic cell release Ca, which turns on thte synthesis of eCB (endocannabonoids) which are lipids, so they can traverse the membranes into the pre-cell and bind to Gi and Go, increasing AMP and reducing glutamate
Term
How is chronic LTP different from acute LTP?
Definition

In chronic LTP, you also have CAMKinaseIV made, activating PKA and CREB, which transcribes genes and causes an increase in AMPA and growth proteins that caues big changes in synapse architecture.

 

 

Acute last minutes, while chronic lasts hours, to days, to weeks

Term
What is GABA made from?
Definition

It is synthesized from glutamate by glutamic acid decarboxylase.

 

GABA can be converted to α-ketoglutarate or succininc acid through GABA-transferase. Basically this means GABA-T tends to decrease GABA levels, even though it can also create it.

Term
What is hyperexcitability?
Definition
When too much GABA is inhibited, leading to increased seizure or epileptic activity
Term
What are the two kinds of GABA receptors?
Definition
  • GABA A: ionotoropic receptors- they let Cl in
  • GABA B: metrabotropic receptors
Term
What is bicuculline?
Definition
This is an antagonist for GABA A receptors; a convulsant drug
Term
Waht is l-baclofen?
Definition
An agonist for GABA B receptors
Term
What is the structure like for GABA A receptors?
Definition
They are pentimers. There are multiple binding sites for other compounds that can modulate the channel
Term
What are the five binding sites of a GABA A receptor?
Definition
  1. The GABA Site: GABA binds here, or bicuculline to inhibit it
  2. The Barbituate Site: agonists will bind here, allowing Cl to go through and hyperpolarize the cell; this is what anesthetics target
  3. The Picrotoxin Site: picrotoxin is another convulsant that can block the channel. However, it is not competitive because it binds at a different site than gabbing, just reducing the conduction of Cl.
  4. The Benzodiazepine Site: compounds that increase channel affinity for GABA bind here, increasing the probability of opening (e.g., valium)
  5. Steroid Site: he didn't care about these, but it seems they can bind both antagonists and agonists (e.g.., anesthetics or anxiogenics)
Term
What are benzodiazepines? Give some examples of commong drugs.
Definition

They are agonists of the GABA A receptors. They have their own unique binding site and are often anxiolytics (decrease anxiety), anticonvulsants, or sleep aids (sedative).

 

Ex: valium, ativan, xanax

Term
What is β-carboline?
Definition
An inverse agonist. It binds to the benzodiazepine site but causes the opposite effects. NOT AN ANTAGONIST. It is anxiogenic and a convulsant
Term
What g-proteins are GABA B receptors coupled to? Think inhibitory. How do these work? Where are they usually found?
Definition

Gi and Go proteins. They open the K channels and block the calcium channels, inhibiting adneylyl cyclase.

 

They are primarily inhibitory autoreceptors

Term
What is GABA-T? What drug targets this?
Definition

GABA-transaminase. It chews up GABA.

 

Vigabatrin can target GABA-T so it doesn't eat up as much, prolonging GABA in the cleft.

Term
What does Tiagabine do?
Definition
It inhibits the reuptake of GABA into the presynaptic cell, prolonging its effect
Term
What is a unique trait of GABA in terms of intercellular effects?
Definition
It is a very diffusible NT, so it is actually able to diffuse over to nearby synapses, even those of glutamatergic cells, supressing other cells and glutamate release.
Term
What is baclofen?
Definition
It is a GABA agonist. It is a muscle relaxant that inhibts glutamate relase through presynaptic GABA B receptors.
Term
What does reserpine do?
Definition
Inhibits the VMAT into the vesicles, depleting DA, NE, and 5-HT stores
Term
What does cocaine do?
Definition
It inhibits DA transporters and blocks reuptake, prolonging DA action (reward)
Term
What do amphetamines do?
Definition
They stimulate the reverse transport of dopamine through their transporters; it is an indirect dopamine agonist
Term
What are selegiline/deprenyl and iproniazid? What is each used for?
Definition

They are MAO inhibitors.

  • Selegiline is used for PD
  • Irponiazid can treat depression, but SSRIs work better
Term
What is bromocyptine?
Definition
It is a D2 agonist: It is used in PD, but also used to suppress prolactin secretion of pituitary tumors
Term
What are holperidol and clozapine?
Definition
They are D2 antagonists. They are used as antipsychotics, and can sometimes have PD-like side effects
Term
What are B-adrenergic antagonists?
Definition
They are an experimental treatment for PTSD. They block negative memory consolidation in the amygdala
Term
What's an example of trcyclic depressant? Why are these not very useful?
Definition
Amitriptyline. Tricyclics are not selective, the block the reuptake of all monoamines, which can be really bad
Term
What is carbidopa?
Definition
It inhibits the function of AADC. However, it cannot pass the BBB, so it only inhibits it in the bloodstream and not in the brain, allowing L-DOPA to get in
Term
Where are the two main projections of dopaminergic neurons?
Definition

The substantia nigra to the striatum, this controls and coordinates motor movements (PD).

 

The VTA to the nucleus accumbens (reward and addiction behavior)

Term
Which dopamine receptors are autoreceptors?
Definition
D1 and D2
Term
Which dopamines receptors are couples to Gs, which to Gi?
Definition

D2,3,4 to Gi

 

D 1,5 to Gs

Term
What is MAO?
Definition
Monoamine oxidase
Term
Where do noadrenergic neurons mostly project?
Definition
Throughout the locus coruleus (zzzzzzzz)
Term
What is the receptor pairings for agonergic receptors?
Definition

Alpha agoneric receptors

a1 are coupled to Gq, a2 are coupled to Gi

 

Beta agonergic receptors

couples to Gs

Term
Which agonergic receptors are autoreceptors?
Definition
Alpha 2 receptors
Term
What does propanolol block?
Definition
They block the beta agonergic receptors, decreasing workload on the heart (b/c they activate Gs)
Term
What does yohimbine block?
Definition
A2 receptors, which can help decrease anxiety by increase NE signaling
Term
What is the only autorecptor for 5HT?
Definition
1D
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