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Neuropharmacology > Barbiturate/Diazepam - GABA signalling > Flashcards

Barbiturate/Diazepam - GABA signalling Flashcards

1
Q

volume tranmission

A

intercellular communication –> occurs in CSF, movement via diffusion
slow transmission
e.g. dopamine

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2
Q

GABAergic neurons

A

release GABA

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3
Q

does GABA or glutamate have a chiral carbon

A

Glu

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4
Q

GAD

A

glutamate decarboxylase

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5
Q

role of glutamate decarboxylase

A

catalyses decarboxylation of glutamate to GABA

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6
Q

2 forms of GAD

A

GAD65

GAD67

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7
Q

where is GAD65 found

A

nerve terminals

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8
Q

where is GAD 67 found

A

throughout cells

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9
Q

GABA biosynthesis

A

GABA is made from glutamate

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10
Q

transporters to get GABA into cells

A

GAT1

GAT3

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11
Q

transporters to get GABA into vesicles

A

VGAT

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12
Q

other use of VGAT

A

also puts Glycine into vesicles

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13
Q

receptors activated by GABA

A

GABA A and GABA B receptors

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14
Q

termination of GABA neurotransmitter action

A

diffusion

uptake by VGAT transporters

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15
Q

ionotropic GABA receptor

A

GABA A

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16
Q

metabotropic GABA R

A

GABA B

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17
Q

properties of GABA A R

A 
ionotropic
pentameric
cys loop on extracellular side
N and C terminals both extracellular
Cl- through central pore
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18
Q

most common GABA A R structure

A

a1 B2 a1 y2 B2

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19
Q

properties of GABA B R

A

metabotropic
7 TM domain
obligate dimer
N-terminus extracellular/C-terminus intracellular

linked to K+ channels via G-proteins

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20
Q

GABA C

A 
sub class of GABA A receptors
therefore also ionotropic
however
insensitive to GABA A antagonist bicucilline
less sensitive to GABAzine
21
Q

GABAzine

A

competitive antagonist

22
Q

ligands binding to orthosteric site

A

bind to GABA site

23
Q

muscimol

A

GABA agonist

psychoactive substance in mushrooms

24
Q

GABA competitive antagonists

A

bicucilline

GABAzine

25
Q

picrotoxin

A

non-competitive antagonist

pore blocker of GABA

26
Q

allosteric ligands

A

bind to a site alternative to GABA site

modulate signalling

27
Q

examples of GABA allosteric modulators

A

benzodiazepines
alcohol
neurosteroids
barbiturates

28
Q

benzodiazepine site

A

between gamma and alpha 1 subunits

29
Q

effect of BDZ on GABA R

A

postivie allosteric modulator
increases effect of GABA
increases frequency of bursts of channel opening

30
Q

physiological effects of BDZ

A

reduce anxiety
anticonvulsant
promote sleep
can be addictive

31
Q

effect of inverse agonists at GABA site

A

decreases effect of GABA

therfore seizures might be promoted

32
Q

competitive antagonist at BDZ-site

A

flumanezil

33
Q

property of BDZ-site ligands that makes them good for focussed therapeutic use

A

some of the ligands have different affinities and selectivity for GABA A receptor subtypes
e.g. BDZ doesnt work on a6 subunits

34
Q

why can barbiturates/neurosteroids kill you at high dose

A

they directly activate receptors and cause respiratory failure

35
Q

effects of barbiturates

A

bind to different site to BDZ
increase duration of bursts of channel opening
positive allosteric modulator

36
Q

where do GABA A receptors clsuter

A

on the post synaptic membrane

37
Q

what causes GABA A R to cluster

A

intracellular proteins

38
Q

therapeutic uses of short/intermediate-acting barbiturates

A

sleeping pills

sedatives

39
Q

which GABA reeceptor has a slow IPSP and why

A

GABA B receptor

mediated by GIRK channels and K+ movement

40
Q

GIRK stands for

A

G-protein coupled Inwardly Rectifying K+ channel

41
Q

mechanism of baclofen to create an IPSP

A

hyperpolarises post-synaptic cells by increasing K+

42
Q

how does baclofen decrease neurotransmitter release from pre-synaptic

A

inhibits Ca2+ channels

43
Q

how does baclofen decrease cAMP production

A

inihbiits adenyl cyclase

44
Q

main function of baclofen

A

selective agonist of GABA B receptors

acts like Gi/o –> decreased cAMP and activates GIRK channels

45
Q

“plus side” of GABA A receptor

A

formed by TM2 and TM3 of the principal (upper) subunit

46
Q

‘minus side’ of GABA A receptor

A

formed by parts of TM1 and TM2 of the complementary subunit

47
Q

4 transmembrane domains of GABA A make up which two subunits

A

principal subunit

complementary subunit

48
Q

does the IPSP change size with successive action potentials

A

if 2 identical presynaptic stimuli are given in rapid succession, the 2nd IPSP will be smaller

Neuropharmacology (14 decks)

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