GABA receptors

Question 1

GABAergic neurotransmission

Answer 1

synthesis:
from glutamate by the enzyme glutamic acid decarboxylase

termination of action:
re uptake or entrance in glia cells

breakdown: GABA-transaminase

glutamine-glutamate/GABA cycle:
transfer of glutamine from astrocytes to neurones and neurotransmitter glutamate or GABA from neurons to astrocytes

Question 2

GABA a

Answer 2

Ionotropic:
heteropentameric ligand gated ion channels that permit the influx of CL- ions to decrease membrane excitability.

mediate the majority of fast synaptic inhibition

1. MUSCIMOL = agonist at GABA binding site
2. BICUCULLINE= antagonist at GABA binding site
3. PICROTOXIN is a channel blocker, a non competitive antagonist
4. BENZODIAZEPINES & BARBITURATES = positive allosteric modulators

Question 3

GABA b

Answer 3

Metabotropic:
expressed on both the presynaptic and postsynaptic terminals where they inhibit neurotransmitter release and induce cell membrane hyperpolarisation.

GABA b agonist: Baclofen
(centrally acting muscle relaxant used in skeletal muscle spasticity)

Question 4

drugs that modulate positively the GABAergic neurotransmission can cause:

Answer 4

1.anxiolytic action (sedation) in lowest dose
2.hypnotic function in moderate dose
3.general anesthesia in even higher dose
4. coma and death in toxic doses
or
5. antiepileptic action
6.skeletal muscle relaxant action
7.amnesia

Question 5

GABA a receptors with a1 subunit

Answer 5

• sedation and hypnotic effect
• the Z hypnotics have preferential affinity to binding sites at this receptor subtype:
  1. zopiclone
  2. zolpidem
  3. zaleplon

Question 6

GABA a receptors with a2 subunit

Answer 6

-anxiolytic effect without sedation