Neurotransmitters

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Neurotransmitters
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Neurotransmitter Criteria
1. Identity
Substance must be found in neurons
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Neurotransmitter Criteria
1. Identity
2. Synthesis
Cell has precursors and enzymes necessary for
synthesis
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Neurotransmitter Criteria
1. Identity
2. Synthesis
3. Release
Must be released from terminals (collect
substance from cleft after nerve stimulation)
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Neurotransmitter Criteria
1. Identity
2. Synthesis
3. Release
4. Receptors
Cross desensitization between substance and
suspected n.t.
Blockade of n.t. action by receptor antagonists
Applicaton of suspected n.t. mimics action of
nerve stimulation
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Neurotransmitter Criteria
1. Identity
2. Synthesis
3. Release
4. Receptors
5. Inactivation
Inactivation mechanism enzymatic degradation
reuptake
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Neurotransmitter Criteria
1. Identity
2. Synthesis
3. Release
4. Receptors
5. Inactivation
6. Pharmacology
Same effect on ion channels p.s.p.s have same
reversal potentials
Same effect on membrane resistance and potential
Applied substances must be effective in
physiological concentrations
Inhibition of degrading enzyme prolongs action
of both
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Neurotransmitter Criteria
1. Identity
2. Synthesis
3. Release
4. Receptors
5. Inactivation
6. Pharmacology
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Acetylcholine Synthesis
CoA
Degradation
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Chemicals that Act on ACh Systems
black widow spider venom
stimulates release of ACh
botulinum toxin
blocks release of ACh
curare
blocks ACh nicotinic receptors
insecticides
AChE inhibitors
atropine as antidote
blocks muscarinic receptors
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Clinical Aspects of ACh Systems
Alzheimers disease
loss of ACh neurons in the basal nucleus of
Meynert
AriceptACh agonist
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Monoamines
single amine (NH2) group
Catecholamines (CAs)
dopamine (DA) norepinephrine (NE,
noradrenaline) epinephrine (EPI, adrenaline)
Indoleamines
serotonin (5-hydroxy tryptamine, 5-HT)
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Catecholamine synthesis
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Serotonin synthesis
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Dopamine Systems
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Norepinephrine Systems
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SystemsSerotonin
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Characteristics of Monoaminergic Systems
Diffuse distribution of targets
Fine, unmyelinated axons
Metabotropic synapses
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Functions of Monaminergic Systems
State phenomena
sleep and arousal
hunger
mood
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Amino Acid Transmitters
Excitatory Amino Acid
Glutamic Acid, or Glutamate
Inhibitory Amino Acids
Gamma Aminobutyric Acid (GABA)
Glycine
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Glutamate Receptor Subtypes
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NMDA receptor binding sites
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http//www.sumanasinc.com/webcontent/anisamples/n
eurobiology/receptors.html
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Glutamate
non-NMDA receptors
NMDA receptors
Na channels open
Ca2 channels open
(Mg2 blockade)
removes blockade
depolarization
Ca2 enters when Mg2 is removed
Ca2dependent K channels open
postsynaptic effects (learning)
reinstates blockade
repolarization
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• Non-NMDA Na channels open, Na
• enters and depolarizes membrane

b. Mg2 blockade of NMDA Ca2 channels removed by
membrane depolarization Ca2 enters

• Ca2 dependent K channels open
• membrane repolarized

d. Mg2 blockade reinstated
a
b
c
d
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GABA receptor binding sites
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Peptide Neurotransmitters
(Often serve hormonal functions as well)
Substance P (P for Peptide)
Principal somatosensory transmitter First peptide
transmitter discovered
Gut hormones
e.g. angiotensin neuropeptide Y
cholecystokinin
Releasing factors for hormones
e.g. tryrotropin releasing hormone
somatotrophin, somatostatin corticotropin
Opiates
Enkephalins, Endorphins
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Diffusible Gases
Nitric Oxide (NO)
Carbon Monoxide (CO)
Heme Oxygenase
Heme
CO biliverdin
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Functions of Diffusible Gas Neurotransmitters
regulate blood flow cerebral peripheral (e.g.
penis)
retrograde messenger Hebbs postulate of learning
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Summary of Neurotransmitters