Transporters

Question 1

Name 5 different neurotransmitter classes

Answer 1

Monoamines (5HT, NA, Adr)
Inhibitory AA (GABA, glycine)
EAA (Glut, aspartate)
ACh
Neuropeptides (Substance P)

Question 2

What are the function of

i) Presynaptic plasma membrane transporters/
ii) Vesicular Transporters

Answer 2

i) terminate synaptic transmission, recycle NT molecules

ii) neurotransmitter storage, prevent intraneuronal metabolism or toxicity.

Question 3

Describe the Na+/Cl- dependant transporters and which NTs they transport.

Answer 3

Transport IAA and MA…

Na+ and Cl- co transport with an IAA or MA…can also extrude 1 K+ (not essential) but will keep it electroneutral.

Question 4

Desrcibe the Na/K+ dependant transporter and which NT they transport

Answer 4

EAA.
2 Na+ co transported with EAA.
1 K+ extruded and 1OH-…electrogenic.

Question 5

What are the names of the neurotransmitter transporters for the following neurotransmitters?

1) DA neurones
2) NA
3) 5HT
4) GABA
5) ACh
6) Glut

Answer 5

1) DAT
2) NET
3) SERT
4) GAT-1
5) Choline-Transporter
6) EAAT-1 - glia
EAAT-2+3 - glia and neurones
EAAT-4 - neurones
EAAT-5 - retinal

Question 6

Describe the glutamate/glutamine shuttle

Answer 6

Glut released into the synaptic cleft. Taken up by EAA1+2 into glia. Converted to gluatmine by glutamine synthase. Transported to pre-synaptic neurone…converted to glutamate by glutaminase.

Question 7

Explain Ca++ independant NT release

Answer 7

Non-vesicular transporter reversal…

SERT transporter can release 5HT or other monoamines.

Question 8

Explain vesicular transport including that of...
VMAT-1, VMAT2
VAChT
VIAAT
Vglut1, Vglut2

Answer 8

EPackages NT into vesicles
Driven by a proton gradient
Maintained by an H+ dependant ATPase.

Question 9

Explain what happens in epilepsy with regards to transporters and potential treatment mechanisms including a drug name.

Answer 9

Recurrent seizures caused by a burst of electrical activity in the brain.

Decreased glutamate uptake into glia (EAA2)…increased glutamate in the synaptic cleft, increased excitation.

So…use GAT blockers (tiagabine) to decrease GABA reuptake and increased inhibition to decrease excitation.

Question 10

Give an example of an SSRI and how it works

Answer 10

Fluoxetine (prozac)

Inhibit 5HT reuptake…to alleviate symptoms of depression

Question 11

Give an example of an antiobesity drug and how it work

Answer 11

fenfluramine

increase 5HT by promoting reverse transport of the reuptake transporter
Promotes feelins of wellbeing and fullness

Question 12

What is the significane of reverse transport in ischemia?

Answer 12

Glutamate is released and contributes to excitotoxic cell death.

Question 13

Cocaine - mode of action?

Answer 13

Blocks DA reuptake

Question 14

MDMA and Ectasy - mode of action?

Answer 14

5HT transporter…promotes reuptake and promotes reverse transport

Question 15

Amphetamines (Speed)

Answer 15

DA transporter (block reuptake and promote reverse transport).