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Neurotransmitters
A. Criteria
1. must mimic presynaptic effects if administered exogenously
2. must be released during activity of presynaptic neuron
3. action must be blocked by same agents that block
natural transmission
Neurotransmitters
B. Activity
1. fast-acting (direct) - ionotropic
- receptor coupled directly to ion channel
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Neurotransmitters
B. Activity
2. slow (indirect) - metabotropic
- receptor coupled to membrane receptor
- activation of second messenger pathways
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Neurotransmitters
B. Activity
2. slow (indirect) - metabotropic
- or modulates opening of channels in response to voltage
changes (neuromodulation)
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Neurotransmitters
C. Classification
1. small molecules
a. acetylcholine (ACh)
b. biogenic amines
c. amino acids
Neurotransmitters
C. Classification
2. neuropeptides (from all areas of nervous system)
a. also from hypothalamus, pituitary, and other organs
b. are often neurosecretory hormones
c. also endorphins and enkephalins
- bind to same receptors as opiates
- endogenous opioids
Neurotransmitters
C. Classification
3. most are highly conserved
4. fast-direct transmitters
- only one type synthesized by individual neurons
a. ACh
- cholinergic neurons (i. e., neuromuscular junction)
- curare is antagonist
Neurotransmitters
C. Classification
- acetylcholinesterase breaks ACh down to acetate and choline
- choline recycled in presynaptic neuron
- blocked by some toxins (Sarin, tetanus)
Neurotransmitters
C. Classification
4. fast-direct transmitters
b. glutamate
- excitatory in vertebrate CNS
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NMDA receptors are ionotropic glutamate receptors
these modulate Ca++ channels
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Neurotransmitters
C. Classification
4. fast-direct transmitters
c. GABA-A (-aminobutyric acid)
- inhibitory at ”glutamate” synapses
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d. glycine
- inhibitory
- can modulate glutamate
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d. glycine
- inhibitory
- some have chloride ionophore function
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Biogenic Amines/Monoamines
- slow, indirect transmission - metabotropic
A. Serotonin - derived from tryptophan
Selective Serotonin Reuptake Inhibitors
Biogenic Amines/Monoamines
B. Catecholamines - derived from tyrosine
- adrenergic neurons
1. epinephrine/adrenaline (hormone and neurotransmitter)
Biogenic Amines/Monoamines
B. Catecholamines - derived from tyrosine
2. norepinephrine/noradrenaline (hormone and neurotransmitter)
- many psychoactive drugs mimic NE
- amphetamines
- cocaine (prevents inactivation of NE)
3. dopamine
Biogenic Amines/Monoamines
C. Release and uptake
1. similar release to ACh
2. rapid inhibition following release
a. reuptake to presynaptic neurons
b. monoamine oxidase in presynaptic neuron
Regulation
Desensitization/Down-regulation
- initially a decrease in affinity
- long-term becomes loss of receptors
Regulation
Super-sensitivity/Up-regulation
- seen in synapses that are rarely used
Regulation
Long-term potentiation
- an increase in the strength of synaptic transmission with
repetitive use that lasts for more than a few minutes
- in hippocampus can be triggered in less than 1 second of
intense synaptic activity
Regulation
Long-term potentiation Model:
1. afferent stimulus causes release of glutamate
2. glutamate binds to NMDA and non-NMDA receptors on
postsynaptic membrane (Na+ influx)
3. EPSP causes removal of Mg++ which normally hinders Na+
and Ca++ influx
4. Ca++ influx leads to activation of postsynaptic protein
kinase, which induces an LTP.
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