Neurotransmitter transport

Question 1

Where are the transporters responsible for NT transport located, and what kind of transporters are they?

Answer 1

In the plasmamembrane and the vesicular membrane. They are symporters. PMTs use Na^+ as a gradient, and VMTs use H^+ as a gradient.

Question 2

What are the different PMT familes, and how many of each are there?

Answer 2

SLC 1 (5), SLC5 (1) and SLC6 (9)

Question 3

Describe SLC1.

Answer 3

Glutamate transporter. Trimer; each monomer has 8 TMs + 1 re-entry loop. The N- and C-terminus are cytoplasmic.

Question 4

Describe SLC5.

Answer 4

Choline transporter. 13 TMs, C-terminal are intracellular, N-terminal are extracellular.

Question 5

Describe SLC6.

Answer 5

GABA, dopamine, glycine and NE (etc.) transporter. 12 TMs (5+5+2 structure), C- and N-terminus are intracellular.

Question 6

What are the different VMT familes, and how many of each are there?

Answer 6

SLC17 (3), SLC18 (3) and SLC32 (1)

Question 7

Describe SLC17.

Answer 7

Glutamte transporter. 12 TMs, C- and N-terminus are cytoplasmic.

Question 8

Describe SLC18.

Answer 8

Acetycholine, dopamine, serotonine, NE, adrenaline and histamine (ect.) transporter. 12 TMs, C- and N-terminus are cytoplasmic.

Question 9

Describe the dopamine transporter (DAT)

Answer 9

Member of the 12 TM Na^+/Cl^- dependent transporter family. Oligomeric (at least dimeric). Mediates reuptak of dopamine in neurons (PMT). Major target for various pharmacologically active drugs and sitmulants (e.g. cocaine, amph)

Question 10

Descripe the functions of cocaine and amph.

Answer 10

Cocaine inhibits the DAT causing an increase in extracellular dopamine conc. Amphetamine competitively inhibits the DAT, and once inside cell it interferes with the vesicular monoamine transporter, resulting in high synaptic conc. of dopamine + uncontrolled release.

Question 11

Describe some of the functions of speed (alfa-methylphenethylamine) and crystal/meth (methamphetamine).

Answer 11

Can induce the release of dopamine, can prevent degradation of dopamine by binding to monoamine oxidase, can bind to and make the DAT work reversible.

Question 12

What is captagon?

Answer 12

It is a prodrug, that is metabolized in the liver to form amph and theophyllin. It is a psychostimulant: you don´t sleep, eat of feel fear.

Question 13

Describe SERT.

Answer 13

Serotonine transporter. 12 TMs, intracellular C- and N-terminus.

Question 14

How does MDMA and ecstacy work?

Answer 14

Acts mainly on SERT inducing an acute increase and delpetion of serotonine. Can also make SERT work reversibly. Depletion happens within 3-6 h, and you feel a burnout for 1-2 d. MDMA and ecstasy also cause irreversible damage on brain: impaired memory, depression, reduced cognative ability ect.

Question 15

How does the 3 generations of antidepressants work respectively?

Answer 15

1. gen: block serotonine degradation
2. gen: TCA, blocking many targets - SERT, DAT, NET. Have many side effects.
3. gen: SSRI = selective serotonine reuptake inhibitor, blocks SERT selectively.