VPT 321: Veterinary Neuropharmacology (2+1)

NEUROTRANSMITTERS IN THE CNS

• Neurotransmitters may be broadly divided into fast neurotransmitters and slow neurotransmitters.
• Fast neurotransmitters operate through ligand gated ion channels (eg. glutamate, GABA) while slow neurotransmitters and neuromodulators operate mainly through G-protein coupled receptors (eg. dopamine, neuropeptides, prostanoids).
• The same agent (eg. glutamate, 5HT and acetylcholine) may act through both ligand gated channels and G-protein coupled receptors.
• Many chemical mediators including glutamate, nitric oxide and arachidonic acid metabolites are produced by glia as well as neurons.
• Many other mediators (eg. cytokine, chemokine, growth factor, steroids) control log term changes in the brain (eg. synaptic plasticity, remodeling etc.) mainly by altering gene transcription.
• Neurotransmitters are also grouped as large molecule neurotransmitters and small molecule neurotransmitters.
  • Acetylcholine, norepinephrine, dopamine, serotonin, gamma-aminobutyric acid, glycine, glutamate and aspartate are the small molecule neurotransmitters located in the CNS.
    • They are synthesised in the cytosol of the presynaptic terminal and cause most of the responses in the CNS.
    • Their actions on receptors usually occur within a millisecond or less after release.
    • After release they are degraded, diffuse out of the cleft or are absorbed by active transport back into the transmitter vesicles.
  • β-endorphin, vasopressin, oxytocin, growth hormone, enkephalin, substance P, somatostatin, cholecyctokinin, angiotensin II and neurotensin are the large group molecule neurotransmitters.
    • They are very potent, slower to act and present in much smaller quantities than the small molecule neurotransmitters.
• The effect of the transmitters on the postsynaptic neuronal membrane is usually to increase or decrease conductance through ion channels.
•  At other times, they stimulate receptor activated enzymes that in turn change the intracellular metabolic processes.
• The neurotransmitter (first messenger) links with receptor proteins of the postsynaptic membrane and stimulates or inhibits an intracellular mediator, the second messenger.
• The second messenger then interacts with various cellular processes to invoke the ultimate action.