Neurotransmitters:
Act on either ligand-gated ion channel receptors
or G-protein coupled receptors
1921: Otto Loewi A factor released from vagus nerve
reduces heart beat ⇒ acetylcholine
criteria as a neurotransmitter
1. A substance should be released when the nerve is stimulated.
2. Application of the substance to the postsynaptic cells should
produces the same effect as nerve stimulation.
3. The presence of the substance in the synapse should be
detected immunocytochemically.
Antibody against the substance (e.g., GABA, ACh, glutamate)
or against an enzyme in the biosynthetic pathway.
These criteria also apply to neuropeptides.
Site of synthesis and transport
Neurotransmitters and neuropeptides are made differently.
Neurotransmitters are synthesized locally and transported
in newly made vesicles in the nerve terminals.
Peptides are synthesized, processed and packed in large
vesicles in the cell body, then axonally transported to the
nerve terminals.
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Neurotransmitter synthesis in the nerve terminals
Three major biosynthetic pathways
Acetylcholine
GABA and glutamate
GABA is formed from glutamate by glutamate decarboxylase (GAD).
GABA used as a transmitter
alternative route: GABA shunt
GABA is destroyed by GABA-glutamate transaminase (GABA-T).
GABA →Succinic semialdehyde → succinic acid :Krebs Cycle
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GABA shunt
Catecholamine synthesis and metabolism
* Dopamine, norepinephrine (noradrenaline) and epinephrine (adrenaline)
are synthesized from tyrosine by a single biochemical pathway.
* Serotonin is synthesized from tryptophan.
* Catecholamines are metabolized by COMT and monoamine oxidase
inhibitors (MAO inhibitors).
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Synthesis and metabolism of serotonin
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Co-localized neurotransmitter and neuropeptide can be
released at different frequency stimulation.
Note
Eserine: AChE inhibitor → prolonged ACh action
Atropin: mAChR antagonist → selective block of ACh action
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