Principles of GABA-ergic Transmission Flashcards Preview

Y2 LCRS 1 - Pharmacology and Therapeutics - Laz > Principles of GABA-ergic Transmission > Flashcards

Flashcards in Principles of GABA-ergic Transmission Deck (36)
Loading flashcards...
1
Q

What are the two main inhibitory amino acid neurotransmitters?

A

GABA

Glycine

2
Q

What are the main excitatory amino acid neurotransmitters?

A

Glutamate
Aspartate
(L-homocysteine – sulphur containing)

3
Q

What type of amino acids are the inhibitory neurotransmitters?

A

Neutral

4
Q

What type of amino acids are the excitatory neurotransmitters?

A

Acidic

5
Q

Why is GABA called GABA?

A

Gamma amino butyric acid

This is because the amino group is on the gamma carbon of GABA

6
Q

Describe the distribution of GABA neurones.

A
Cerebral cortex 
Cerebellum 
Hippocampus  
Corpus striatum  
Hypothalamus  
Dorsal horn of spinal cord  
Relatively little in the PNS
7
Q

Describe the morphology of GABA neurones.

A

They are generally short inhibitory interneurons

8
Q

Where do you find longer GABA tracts?

A

Striato-nigral

Cerebellar

9
Q

What is the main action of GABA neurones?

A

Widespread inhibitory action in the CNS

10
Q

What are the main functions of GABA neurones in terms of CNS activity?

A

Emotional control
Motor control
Extrapyramidal activity
Endocrine function

11
Q

What is the precursor for GABA and what enzyme converts it to GABA?

A

Glutamic acid

Glutamic acid decarboxylase (GAD)

12
Q

Where is this enzyme found?

A

This enzyme is exclusive to GABA nerve terminals – it is a marker for GABA neurones

13
Q

What product of the Krebs’ cycle gives rise to glutamate?

A

Alpha-oxoglutarate

14
Q

How is GABA broken down?

A

Initially by GABA-T (GABA transaminase) to succinic semialdehyde
Succinic semialdehyde is broken down by succinic semialdehyde dehydrogenase (SSDH) to succinate
Succinate then enters the Krebs’ cycle

15
Q

Describe the release of GABA from GABAergic nerve terminals.

A

Calcium-mediated exocytosis

16
Q

What are the two main GABA receptors and why type of receptorsare they?

A
GABA-A = type 1 – ionotropic  
GABA-B = type 2 – metabotropic
17
Q

How is GABA inactivated?

A

By reuptake

18
Q

What are the uptake mechanisms dependent on?

A

Sodium dependent

Energy dependent

19
Q

Where are the transport proteins for GABA found?

A

Presynaptic neurones

Glial cells

20
Q

What type of enzymes are the enzymes that break down GABA?

A

Mitochondrial enzymes

21
Q

What type of enzyme is GAD?

A

Cytoplasmic enzyme

22
Q

Name two drugs that are used as anti-convulsants that decrease the metabolism of GABA.

A
Sodium valproate (acts on GABA-T and SSDH (but more so on SSDH)) 
Vigabatrin (selective GABA-T inhibitor)
23
Q

Where are GABA-A receptors found?

A

Postsynaptic

24
Q

Describe the structure of GABA-A receptors.

A
They are ionotropic receptors (type 1) 
They have a pentameric structure consisting of the following subunits:
 2 x alpha 
 2 x beta 
 1 x gamma
25
Q

What is the mechanism of action of GABA-A receptors?

A

GABA binding causes opening of the chloride channel leading to chloride influx
This causes hyperpolarisation of the postsynaptic neurone (inhibitory post-synaptic potential)
This causes inhibition of firing

26
Q

Name two agonists of GABA-A.

A

GABA

Muscimol

27
Q

Name two antagonist of GABA-A

A

Bicuculline (competitive antagonist)

Picrotoxin (non-competitive antagonist)

28
Q

What effect do the antagonists have?

A

They are convulsants

They are used experimentally but not therapeutically

29
Q

Where are GABA-B receptors located?

A

Presynaptic

30
Q

What is the effect of GABA-B?

A

It is the negative feedback receptor for GABA release (similar to the effect of alpha-2 receptors on noradrenaline release)

31
Q

What are the two different terms used to describe GABA-B receptors that regulate GABA release and other neurotransmitter release (e.g. dopamine)?

A

Autoreceptors – when they regulate GABA release

Heteroreceptors – when they regulate the release of other neurotransmitters

32
Q

Describe the mechanism of action of GABA-B receptors.

A

G protein linked receptor
Causes a decrease in calcium conductance
Reduction in neurotransmitter release
Stimulation of GABA-B also causes a reduction in cAMP

33
Q

Name two agonists of GABA-B receptors.

A

Baclofen

GABA

34
Q

Name an antagonist of GABA-B receptors.

A

Saclofen (competitive antagonist)

35
Q

What can GABA-B receptor agonists be used for?

A

Muscle relaxant and spasmolytic
Mechanism – reduced GABA release in the spinal cord and reduced activation of alpha motor neurone output causes relaxation of skeletal muscles
This reduces spasticity

36
Q

Describe how G-protein coupling works.

A

GABA binds to the GABA receptor and changes its conformation so that it can bind the alpha subunit of the G protein
The alpha subunit normally has GDP bound to it, when it binds to the receptor it exchanges GDP for GTP
The alpha-GTP subunit is active at the target
The alpha subunit breaks down GTP to GDP, which then inactivates it