GABA + GABA R

Question 1

From which substarte are GABA synthesized?

Answer 1

Glutamate, by glu decarboxylase

Question 2

GABA is the major…

Answer 2

main inhibitory neurotrasmitter in the brain

Question 3

How many different types of GABA Rs are there, and are they ionotropic or metabotropic?

Answer 3

3 different types, A + C are ionotropic and B is metabotropic

Question 4

What are the general topology of the iGABARs?

Answer 4

Similar to glyR (Cys-loop family): pentameric, each monomer have 4 TMs, both N- and C-terminal are extracellular, cys-loops on N-terminal. TM2 forms the pore. Binding site between the subunits

Question 5

What are the agonists of the GABA Rs except for GABA?

Answer 5

Type A: muscimol, type B: baclofen, type C: none

Question 6

What are the antagonist, PAM and pore blocker of the type A GABA R?

Answer 6

Antagonist: bicuculine, PAM: valium, librium, ethanol and other sedatives, pore blocker: picrtoxin (also for type C)

Question 7

How many receptors are there of each type?

Answer 7

A: at least 30, B: 2, C: at least 20

Question 8

What are the topoogy of the type B receptor?

Answer 8

Heterodimeric, composed of GBR1 and -2. GRB1 is responsible for ligand binding, GRB2 is coupled to the G-protein (Gi)

Question 9

Which ion are the iGABARs permeable to?

Answer 9

Cl^-

Question 10

Which diseases are the GABA Rs involved in?

Answer 10

Spasticity and psychiatric diseases like anxiety and insomnia

Question 11

How is the GABA A R involved in psychiatric dieases?

Answer 11

The PAMs are anxiolytic and hypnotic

Question 12

Explain how baclofen can be used as a medicine for spasticity.

Answer 12

Spasticity is clinically defined as the loss of inhibition of motor neurons causing excessive muscle contraction. Baclofen is an agonist of the GABA B R inducing inhibition of motor neurons