Term
Criteria for Neurotransmitters
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Definition
1. Synthesis and storage in neurons
2.Calcium-dependent release upon depolarization of axon terminals
3.Inactivation by reuptake or catabolism
4.Activation of pharmacologically defined postsynaptic receptors
5.Synaptic mimicry-application of substance exogenously mimics the
action of nerve stimulation
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Term
Neuropharmacological agents can act to alter: |
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Definition
1.Neurotransmitter synthesis and storage in neurons
2.Neurotransmitter release from nerve terminals
3.Direct postsynaptic effects of neurotransmitters
(via activation or blockade of postsynaptic receptors)
4.Neurotransmitter inactivation by reuptake or catabolism
5.Neuronal responsiveness to receptor activation
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Term
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Definition
Acetylcholine
Catecholamines
lDopamine
lNorepinephrine
lEpinephrine
Serotonin
Histamine
Glutamate
GABA
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Term
Classification of Neurotransmitters |
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Definition
Amines (classical neurotransmitters)
acetylcholine, dopamine, norepinephrine, serotonin
Amino Acids
glutamate, glycine, GABA, aspartate, taurine
Neuropeptides
CCK, NPY, enkephalin, TRH, SP, leptin, NGF
Lipid Mediators
prostaglandins, thromboxanes, ceramide
Gases
NO, CO
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Term
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Definition
Ligand-gated (or direct-gated or ionotropic) channel receptors
ion channels open upon agonist binding
electrical response is fast and of short duration
Indirect-gated (or metabotropic) receptors
channels linked to second messengers or G-proteins
opens or closes channels,
causing slow and long electrical response initiates intracellular enzyme cacades amplifies signal interacts with other second messenger pathways modifies gene transcription
Tyrosine kinase receptors
for peptidergic growth factors
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Term
NT receptors, general properties |
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Definition
Membrane-spanning proteins located on dendrites, soma, axon terminals. Allows neurons to communicate with chemical signals.
Inhibitory receptors frequently located on soma: hyperpolarization.
Excitatory receptors frequently located on dendrites: depolarization.
Modulatory receptors, located on terminals, do not affect excitability,
but can affect amount of NT released by local terminal.
Activity can stabilize receptors in membrane.
Down-regulation can occur after increased activity.
Up-regulation can occur after decreased activity.
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Term
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Definition
1.Brain: basal forebrain and effector neurons that project to PNS
2.Interneurons: target of benztropine in Parkinson’s
3.Lower motor neurons projecting to neuromuscular junction
4.Sympathetic and parsympathetic preganglionic neurons
5.Parasympathetic postganglionic neurons
Degraded by acetylcholinesterase in synapse. Choline is reuptaken for recycling. Reuptake blocked by hemicholinium.
Cholinesterase inhibitors used for Alzheimer’s and myasthenia gravis.
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Term
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Definition
NIGROSTRIATAL: Substantia Nigra (pars compacta) to
Caudate, Putamen (Striatum) and Globus Pallidus
Motor Functions - Involved in Parkinson's Disease
MESOLIMBIC: Ventral Tegmental Area (VTA) to
Striatum, Septum, Amygdala, Olfactory Tubercle
Involved in Locomotor Activity and Reward
MESOCORTICAL: Ventral Tegmental Area (VTA) to
Prefrontal and Cingulate Cortices
Cognitive Function
TUBEROINFUNDIBULAR: Hypothalamic Arcuate Nucleus
to Median Eminence and Posterior and
Neurointermediate Lobes of Pituitary
Regulation of hormone release, esp. Prolactin
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Term
Major Catecholamine Catabolites |
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Definition
for Dopamine:
•Homovanillic acid (HVA)
•3,4-Dihydroxyphenylacetic acid (DOPAC)
•3-Methoxytyramine (3MT)
for Norepinephrine:
•Normetanephrine (NM)
•3,4-Dihydroxyphenylethyleneglycol (DHPG)
•3-Methoxy,4-hydroxyphenylethyleneglycol (MHPG)
•Vanillylmandelic acid (VMA) - largely peripheral
for Epinephrine:
•Metanephrine (3-Methoxyepinephrine)
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Term
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Definition
Uptake I (Reuptake)
-Very specific, high-affinity transporters
-Limited capacity
-Absolute requirement for Na+
-Only found in neurons releasing that neurotransmitter
-The mechanism for re-uptake
Uptake II
-Specific, but lower affinity than Uptake I
-High capacity
-Does not require Na+
-Found in both neurons and glia
-An overflow mechanism
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Term
Additional notes on Dopamine (DA)
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Definition
1.L-Dopa crosses blood-brain barrier, dopamine does not.
2.Inactivated by reuptake, which is blocked by cocaine
and methylphenidate.
3. Degradation: MAO intraneuronal; COMT extraneuronal.
4.Metabolite HVA in CSF can reflect disease state,
e.g. low in Parkinson’s
5. Lithium interferes with DA neurotransmission.
6. Agonists: bromocriptine, ropinirole, pramipexole
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Term
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Definition
As the dose is Increased:
•Displaces catecholamines from synaptic vesicles
•Inhibits transporters, and hence reuptake
•Inhibits MAO
•a-Receptor agonist
NE > DA >> 5-HT
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Term
Additional notes on Norepinephrine (NE) and Serotonin (5-HT)
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Definition
NE Agonists: ephedrine, phenylephrine, propanolol
NE function in CNS: arousal, fear, motivation, pleasure
MAO inhibitor antidepressants potentiate both
catecholaminergic and serotonergic transmission.
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Term
Notes on Amino Acids Glutamate, GABA, Glycine
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Definition
glutamate acts on ligand-gated channel (ionotropic) receptors to
mediate fast excitatory transmission and G-protein coupled
(metabotropic) receptors to mediate slower and more complex
responses. Inactivation by glial uptake. Glutamate excitotoxicity
causes neurons to undergo apoptosis.
GABA is major CNS inhibitory NT. Inactivated by reuptake into
neurons and glia. Valproate is an anticonvulsant to control seizures,
stimulates GAD and inhibits degradation. Altered GABA function:
basal ganglia disorders, seizures, schizophrenia, sleep disorders.
GABA-A receptors are GABA-gated Cl- channels.
Glycine is inhibitory NT in brainstem and spinal cord. Strychnine is
antagonist. Tetanus toxin is carried into inhibitory neurons and
prevents NT release, results in excess motor activity, muscle spasm,
potentially respiratory failure and death.
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Term
Notes on Peptides and Nontraditional NTs
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Definition
Peptides:
More than one neuroactive peptide may be formed from
larger precursor (proenkephalin). Made in cell body and
packaged in large dense-core vesicles. Often co-
localized in terminals with small-molecule NTs.
Modulate action of NTs. Tachykinins
(substance P), secretins (VIP), insulins, pituitary peptides, opioids,
neurotrophic factors. Peptides travel farther and are more potent.
Nitric oxide is gas with short duration of action. Binds and activates
intracellular guanylyl cyclase. Can act as a retrograde NT.
Functions: relaxation of blood vessels and synaptic plasticity.
Anandamide is cannabinoid receptor ligand that is formed by
cleavage of membrane-bound phospholipid precursor.
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Term
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Definition
Neurotoxins
Botulinum toxin: blocks neuromuscular and autonomic transmission
by blocking ACh release by cleaving vesicle proteins. Most lethal
toxin known. Descending paralysis: blurred vision, impaired speech,
swallowing, breathing, dry mouth, muscle weakness. Death by paralysis
of respiratory muscles. Therapeutic use: control focal muscle spasm
in cervical dystonia.
Tetanus toxin: released into CNS after retrograde transport by peripheral
nerves. Cleaves vesicle proteins in inhibitory neurons. Muscle spasms and
tetanus from loss of motor neuron inhibition.
alpha-larotoxin (black widow spider): releases NTs at neuromuscular junction
until stores are depleted. Hyperexcitability, muscle spasms, rigidity, paralysis.
Tetrodotoxin (puffer fish): blocks voltage-gated sodium channels.
Numbness, paralysis, possible respiratory failure.
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