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What is a neurotransmitter?
Secreted factor from neurons
Limited to a specific population
Regulated synthesis, enzyme
Produce a measurable effect
Bind a specific, saturable receptor
Release in response to stimulus from
axon terminal
• Storage in vesicles
• Degradation and/or re-uptake
Alternative transmitters
Purines, nucleosides: ATP and adenosine
Gases: NO and CO
Fatty acid metabolites, endocannabinoids
Neurotrophic factors: NGF, BDNF, etc.
D-amino acids: D-serine
Functions of ATP
• Released in response to hypoxia,
mechanical stress, injury
• Recruits microglia and macrophages
• Spinal nociception-neuropathic pain
• Regulates breathing in response to pH
• Short half life, most degraded to
adenosine in < 1 sec
Functions of adenosine
• Released especially by stressed cells
– Seems non-exocytotic, non-Na+ or Ca2+
– Stimulated release of ATP is TTX sensitive and
Ca2+ dependent
• Increases oxygen delivery by dilating
• Decrease cell energy usage (reduce cellular
oxygen requirements)
– Decrease firing rate, NT release, etc.
Promotes sleep
Adenosine transport
Soluble gasses
Carbon Monoxide
Fatty acid derivatives
Glial derived steroids
Serine racemase
Knockouts of all these NTs, and their receptors, are lethal.
Acute roles for NT in adult brain
• Application of NT to brain leads to
seizure activity (coordinated neural
• NGF application to PNS leads to painful
• Neuronal activity likewise regulates NT
synthesis (BDNF and NGF by seizure)