2016.03.22 neurotransmitters
- 2. OTTO LOEWI’S EXPERIMENT Vagosstoff – acetylcholine from isolated heart.
- 3. Synthesis of neurotransmitter at nerve terminal Storage within synaptic vesicle Release of chemical into synaptic cleft Regulation both physiological & pharmacological, at synaptic cleft can lead to influence on somatic / visceral motor activity and also emotions & behaviour.
- 4. Small molecule neurotransmitters: amino acids ( glutamate, gamma aminobutyric acid, and glycine), acetylcholine, monoamines ( norepinephrine, epinephrine, dopamine, and serotonin), and ATP Large molecular transmitters: neuropeptides (substance P, enkephalin, vasopressin). Neuropeptides are co-localized with small molecular neurotransmitters. Neurotransmitters classification:
- 5. Neurotransmitters act on receptors which are ion channels RECEPTORS: i) Are in sub-population, alpha and beta adrenergic receptors for adrenaline ii) Autoreceptor is on pre-synaptic membrane providing feedback control. iii) Receptors undergo desensitization / unresponsiveness to transmitters REUPTAKE OF NEUROTRANSMITTER -by transporters in presynaptic membrane -packing into vesicles by transporters on vesicular membrane -reuptake when inhibited prolongs transmitter action -cocaine inhibits dopamine uptake -antidepressants are inhibitors of amine transmitter uptake - -Hypoxia prevents glutamate uptake- excitotoxin (Ca influx)
- 6. Glutamate: - acts on AMPA, Kaniate & NMDA receptors - on AMPA receptors leads to Na influx & K efflux, net effect it causes excitation of post-synaptic neurons. - kaniate & NMDA receptors, when have altered subunits permit Na & Ca influx - Ca influx causes excitotoxin Excitotoxin: - in the face of hypoxia & hypoglycymia - when cerebral artery is occluded, stroke
- 7. GABA: - inhibitory neurotransmitter - causes chloride influx & hyperpolarization - is present in interstitial fluid & increases signal to noise ratio - benzodiazepines (diazepam) is used to alleviate anxiety, relax muscles
- 8. Glycine: - inhibitory neurotransmitter, chloride influx - along with glutamate on NMDA receptor causes Na influx and excitation
- 9. Acetylcholine: - in autonomic ganglia, parasympathetic target gland junction, neuromuscular junction - acts on nicotinic / muscarinic acetylcholinergic receptors - receptors are nicotinic in motor end plate of muscles - acetylcholinergic receptors are involved in sleep- wake cycle, and learning and memory
- 10. Monoamines: - norepinephrine, epinephrine, dopamine - monoaminergic neurons rich in locus coerulus - reuptake when inhibited by amphetamine / cocaine leads to euphoria - monoamine oxidase (MAO) breaksdown monoamines - MAO inhibitors are used in treatment of depression
- 11. Serotonin: - serotonin reuptake inhibitors - used as antidepressants
- 12. Substance P: - sensory afferent neurons in dorsal horn - pain neurotransmission
- 13. Encephalin - act on afferent sensory neurons to block Ca influx and prevent glutamate exocytosis in pain pathway - also act on spinothalamic neurons to cause K efflux and hyperpolarization in pain pathway