Shared Flashcard Set

Details

1.23 Signal Transduction
by Dr. Nichols
59
Pharmacology
Professional
01/23/2012

Additional Pharmacology Flashcards

 


 

Cards

Term
What is the difference between an effector and a second messenger?
Definition
effector= enzymes and proteins
molecules= 2nd messengers
Term
Name some of the endogenous ligands that bind GPCRs?
Definition
neurotransmitters (5-HT, dopamine, ACh, glutamate, opioid, norepi, etc.), vasopressin, somatostatin, oxytocin, TSH, postaglandin receptors
Term
Where is the COOH domain? the NH3 domain?
Definition
NH3= extracellular
COOH= intracellular
Term
List the three main types of G proteins.
Definition
alpha, beta, gamma
Term
Name the different alpha subunit families.
Definition
alpha s, alpha 12, alpha i, alpha q
Term
Gaq pathway=
Definition
PLCB -> PIP2->DAG -> PKC
OR
PIP->IP3 -> Ca2+
Term
Describe the Gai pathway.
Definition
PLA2-> AA
OR AC --> cAMP -> PKA -> CREB
Term
Describe the Gas pathway.
Definition
AC -> cAMP -> PKA -> CREB
Term
Describe the Ga13 pathway.
Definition
Ga13 -> rho/arf -> PKD -> phosphatidylcholine -> choline and phosphatidic acid -> AA
Term
Describe the alpha1 receptor pathway.
Definition
Gq->PLC -> IP3 and DAG from inositol phospholipids. Gq linked receptor store operated calcium channel. Increases intracellular calcium. Aclcium calmodulin stimulates myosin light chan kinase-> contraction
Term
Name an alpha 1 agonist?
Definition
phenylephrine
Term
name an alpha 1 antagonist
Definition
prazosin
Term
How do alpha 2 receptors work?
Definition
alpha 2 engages Gi and G0 classes of G protein. Gi/0 inhibit adenylate cyclase, reducing cAMP levels; Gi/o increase Ca influx. decrease in cAMP allows calcium-calmodulin stimulation of MLCK activity, causing contraction
Term
Name an alpha 2 agonist.
Definition
clonidine
Term
What effect on vasculature do presynaptic alpha 2 receptors have?
Definition
indirectly cause vasodilation when NE or EPI binds to the alpha 2 receptor by inhibiting release of NE
Term
What other effects do alpha 2 receptors have other than contraction of vascular smooth muscle?
Definition
indirect effects that lead to vasodilation, aggregation of platelets and decreased insulin secretion
Term
Describe the mechanism of beta receptos?
Definition
activate Gs -> AC -> cAMP (voltage gated Ca channels) -> PKA directly phosphorylates proteins (troponin I) essential for cardiac muscle contraction, stimulates opening of voltage gated Ca channels, inhibits uptake of Ca into cellular stores and cAMP is hydrolyzed by phosphodiesterases
Term
What type of receptor is beta 1?
Definition
Gs (stimulatory)
Term
What are the effects of beta 1 activation on the heart?
Definition
positive, ionotropic, chronotropic and dromotropic effects
Term
Name a beta 1 agonist.
Definition
dobutamine
Term
Name a beta 1 antagonist.
Definition
atenolol
Term
What type of G protein is beta 2 receptor?
Definition
Gs
Term
What is the function of an activated beta2 receptor?
Definition
relaxes vascular, bronchial, GI, and GU smooth muscle; stimulates uptake of potassium into skeletal muscle, stimulates glycogenolysis and gluconeogenesis in the liver
Term
Name a beta 2 agonist.
Definition
terbutaline
Term
Name a beta 2 antagonist.
Definition
propranolol
Term
What type of G protein is beta3?
Definition
Gs
Term
What is the function of beta 3 receptors?
Definition
PKA stimulates lipase activity in adipose tissue
Term
What type of receptor is an M1 receptor?
Definition
Gq
Term
Name an M1 antagonist?
Definition
pirenzipine
Term
Describe the signaling pathway of M2 receptors?
Definition
Gi/o: inhibition of adenylate cyclase and decreased cAMP; activation of K+ channels (e.g. heart), inhibition of Ca2+ channels (e.g. heart)
Term
What effects does M2 receptor activation have on the heart?
Definition
reduced PKA phospohrylation of troponin I and ionic changes cause engative ionotropic and chronotropic effects on the heart
Term
What receptor is M2 the antagonist of?
Definition
beta 1
Term
Name an M2 receptor antagonist.
Definition
tripitamine
Term
Describe the mechanism of an M3 receptor?
Definition
Gq: activation of PLC, production of IP3, and increased intracellular calcium, similar to M1
Term
What are the physiological effects of M3?
Definition
secretion (bronchial, sweat and salivary, gastric acid). Indirect effect on vasculature: increased synthesis of NO and PGI2 in vascular endothelium causing vasodilation)
Term
Name an M3 antagonist
Definition
Darifenacin
Term
Name a non-selective antagonist ofall the muscarinic receptors.
Definition
atropine
Term
What are the different sensitivities for NE vs EPI in the different beta receptors?
Definition
B1 myocardium (EPI=NE), B2 smooth muscle (E, no affinity for NE), B3 adipose (NE>E)
Term
How does beta 1 cause contraction while beta 2 cause relaxation?
Definition
PKA phosphorylates contractile machinery proteins e.g. troponin 1 in beta1

PKA phosphorylation of MLCK inhibits myosin function in beta 2
Term
What is the effect of low versus high epi in vessels in skeletal muscles?
Definition
low, beta 2 wins= increased Gs, cAMP = vasodilation
high, alpha 1 wins= increased Gq, Ca2+, overcomes cAMP effects, vasoconstriction
Term
Should you use a low or high dose epi to treat shock?
Definition
high
Term
The sum of what two autonomic receptors determines cardiac output?
Definition
beta1 (Gs) and M2 (Gi)
Term
What are possible mechanisms to treat cardiac symptoms of beta blocker overdose?
Definition
glucagon Gs coupled receptor; PDE inhibitor
Term
What do arrestins do?
Definition
halt the GPCR resonse
Term
T/F Arrestin signaling can occur independent of G protein signaling.
Definition
true
Term
Antagonists of GPCRs can activate waht molecules?
Definition
arrestins
Term
How does carvedilol work?
Definition
beta adrenergic antagonists that acitvates beta 2 arrestin to treat heart failure
Term
Name some examples of TRKs.
Definition
insulin receptor, EGF, VEGF, PDGF, FGF, TNFR
Term
Which receptor can bind to ligands that are proteins attached to other cells for cell-to-cell signaling?
Definition
tyrosine receptor kinases
Term
How do tyrosine receptor kinases transduce a signal?
Definition
ligand binds, receptor dimerizes and phospohrylates itself; phorpohrylated tyrosines provide docking sites for SH2 domains that exist in many signaling molecules
Term
Describe the TRK/RAS pathway.
Definition
TRK, GRB2, SOS, RAS-GDP --> RAS-GTP which phosphorylates RAF, which phosphorylates MED, which phosphorylates ERK
Term
How can Gai/o crosstalk with TRK?
Definition
gamma beta can create Src affecting TRK
Term
What aa is NO produced from?
Definition
arginine
Term
T/F NO can act intra or intercellularly.
Definition
true
Term
How does NO cause vasodilation?
Definition
stimulates guanylate cyclase to produce cGMP
Term
How does the endothelial cell know to produce NO to produce vasodilation of the surounding vascular smooth muscle?
Definition
ACh binds to M3 which increases Ca activating eNOS
Term
State the equation by which NO is made.
Definition
L-arginine + O2 + NADPH2---eNOS----> H2O + L-citrulline + NO
Term
Sildenafil works by inhibiting...
Definition
PDE5
Term
What is functional selectivity?
Definition
intrinsic property of the drug/receptor interaction whereby different drugs can activate or inactivate one or multiple effector pathways from a single receptor to differentially influence physiology
Supporting users have an ad free experience!