36. Drug Action on GABA and Receptors

Question 1

Describe GABA.

Answer 1

Gamma-Amino Butyric Acid, an amino acid
* GABA is a chief inhibitory neurotransmitter in the CNS
* principle role: reducing neuronal exicitability throughout the nervous system + regulate muscle tone

Question 2

What is the main location of GABA in the CNS?

Answer 2

Amygdala

Question 3

What is the function of GABA in the CNS?

Answer 3

Excitatory neurons in the amydgala fire to send excitatory signals to other areas of the brain.
* result: anxiety and fear

GABA can be released to inhibit excitatory signals
* result: calming effect

Question 4

Where is GABA synthesized?

Answer 4

GABA is unable to cross the BBB –> must be synthesized from glutamate in the neurons in the brain.

Question 5

Explain the human diseases associated with abnormal levels of GABA.

Answer 5

• epilepsy seizure
• anxiety disorder
• schizophrenia

Question 6

Explain the biosynthesis of GABA: Step 1.

Answer 6

In the mitochondrion, glutamine (Gln) is converted to glutamate (Glu) by glutaminase.

Question 7

Explain the biosynthesis of GABA: Step 2.

Answer 7

GABA is synthesized from glutamate by glutamic acid decarboxylase (GAD).

Question 8

Describe the process of GABA storage: Step 3.

Answer 8

GABA is uptake into vesicles by vesicular GABA transporter (vGAT).

Question 9

Describe the release process of GABA: Step 4.

Answer 9

Under stimulation by Ca2+, vesicles infuse with presynaptic membrane and release GABA to synaptic cleft during exocytosis.

Question 10

Describe the process of GABA reuptake: Step 5/6.

Answer 10

GABA is reuptake by GABA transporter (GAT) back to vesicles in presynaptic neuron for reuse.
* GABA is uptake into glial cells via GAT

Question 11

Describe the degradation process of GABA: Step 7/8.

Answer 11

• In the glial cells, GABA is converted to glutamate by GABA transminase (GABA-T) in mitochondrion.
• Glutamate is converted to glutamine by glutamine synthase.

Question 12

Describe the process of glutamine reuptake: Step 9.

Answer 12

Glutamine is transported back to presynaptic neuron by glutamine transporter.
* glutamine can be reused for GABA synthesis

Question 13

Describe the difference between GABA and glutamate.

Answer 13

GABA - calming neurotransmitter
Glutamate - excitatory neurotransmitter

Question 14

Explain the effects of too much glutamate.

Answer 14

Anxiety, perserervating, restlessness, migraines, tics, motor stereotypies (flapping/stimming)

Question 15

Explain the effects of too much glutamate.

Answer 15

Anxiety, perserervating, restlessness, migraines, tics, motor stereotypies (flapping/stimming)

Question 16

Tiagabine
Drug action:
Target protein:
Therapeutic indication:

Answer 16

Drug action: inhibition of reuptake
Target protein: GABA transporter (GAT)
Therapeutic indication: anticonvulsant

Question 17

Vigabatrin
Drug action:
Target protein:
Therapeutic indication:

Answer 17

Drug action: inhibition of degradation
Target protein: GABA transaminase (GABA-T)
Therapeutic indication: epilepsy seizure

Question 18

Explain the process of GABA signaling in the postsynaptic neuron.

Answer 18

GABAs move across the synaptic cleft and bind to GABA receptors in postsynaptic neuron for signaling

GABA receptors:
* GABAaR: ionotropic receptors
* GABAbR: metabotropic receptors

Question 19

Explain what happens when GABAaR is activated by GABA.

Answer 19

Results in translocation of Cl- ions into postsynaptic neuron, making the cell hyperpolarize and inhibiting action potentials.
* Cl- ions make the neuron harder to be stimulated by other neurotransmitters, thus slowing down its activity and making the person feel more relaxed.

Question 20

Explain what happens when GABAbR is activated by GABA.

Answer 20

Results in release of G-coupled proteins –> activate K+ ion channel to effluc K+ ions out of the postsynaptic neuron –> hyperpolarization of the cells.
* also results in inhibition of Ca2+ uptake

Question 21

Muscimol
Drug action:
Target protein:
Therapeutic indication:

Answer 21

Drug action: Agonist
Target protein: GABAaR
Therapeutic indication: research on for epilepsy

Question 22

Gaboxadol
Drug action:
Target protein:
Therapeutic indication:

Answer 22

Drug action: agonist
Target protein: GABAaR
Therapeutic indication: research only

Question 23

Bicuculline
Drug action:
Target protein:
Therapeutic indication:

Answer 23

Drug action: antagonist
Target protein: GABAaR
Therapeutic indication: research only for epilepsy

Question 24

GHB
Drug action:
Target protein:
Therapeutic indication:

Answer 24

Drug action: Agonist
Target protein: GABAbR
Therapeutic indication: narcolepsy

Question 25

Baclofen
Drug action:
Target protein:
Therapeutic indication:

Answer 25

Drug action: agonist
Target protein: GABAbR
Therapeutic indication: spastic movement disorders + alcohol withdrawal

Question 26

Phenibut
Drug action:
Target protein:
Therapeutic indication:

Answer 26

Drug action: agonist
Target protein: GABAbR
Therapeutic indication: anxiety and insomnia

Question 27

Answer 27

e. amygdala

Question 28

Answer 28

C. GABA transporter on presynaptic membrane.

Question 29

Answer 29

b. seven-pass transmembrane domains

Question 30

Answer 30

d. efflux of Cl- ions from postsynaptic neuron
* GABAaR receptors trigger influx of Cl- ions into postsynaptic neuron,

Question 31

Answer 31

a. activation of Ca2+ channels
* inhibits Ca2+ uptake
* activate K+ ion channels

Question 32

Answer 32

d. bicuculline
* GABAaR antagonist