2016.03.22 neurotransmitters

1. 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