Neurotransmitters and receptors

Question 1

What are the mechanisms of NT action

Answer 1

1. Direct interaction w membrane ion channel
   - NT binds directly to ion channel, having immediate effect.
   - eg. GABA and glycine receptors.
2. Indirect interaction w an ion channel via G protein.
   - The G Protein links the receptor to the ion channel.
   - NT binds receptor - G protein intermediary - ion channel
   - eg. mACh receptors in heart muscle control potassium channels via g-proteins
3. Indirect interaction with an ion channel via a G protein and an intracellular second messenget.
   - NT binds receptor - G protein linked to receptor stimulates the production of an intracellular 2nd messenger - effect.
   - eg. Beta receptors linked to adenylate cyclase + cAMP via a stimulatory g protein

Question 2

What is the effect of excitatory and inhibitory NTs

Answer 2

1. Excitatory = open Na and Ca channels
2. Inhibitory = open K and Chloride channels

Question 3

List 7 important neurotransmitters

Answer 3

1. Acetylcholine
2. Catecholamines (NA, Adrenaline, dopamine)
3. Seretonin
4. Histamine
5. Amino Acids - GABA, glycine, glutamate
6. Purines - Adenosine, ATP
7. Neuropeptides - Met-enkephalin, leu-enkephalin, dynorphin, substance P, calcitonin gene related peptide.

Question 4

G Proteins structure

Answer 4

Large heterotrimeric proteins
Consist of alpha, beta, gamma subunits.
Subunits act as transducers to bring about intracellular changes from extracellular signal.
Alpha subunit can bind to both GDP and GTP
- Inactive GDP in bound to the alpha subunit at rest

Question 5

G Protein Coupled Receptor Function

Answer 5

Cell surface receptors bind a ligand on the extracellular side, results in conformational change that activates the G protein on the intracellular side.
- GPCR activated = GDP exchanged for GTP and the alpha subunit disassociates from the b and y chains.
- The active a-GTP complex then affects ion channels or 2nd messenger systems.
- G proteins are inactivated when the alpha unit hydrolyses GTP to GDP and re-joins the by complex. (self limiting step)

Signal amplification can occur
- one g protein can activate many intermediate messengers.

Question 6

Classify G Proteins

Answer 6

G Proteins are classified by their alpha subunits.

1. Gs
   - Activated by: adrenalin, noradrenaline, histamine, glucagon
   - Outcome: G protein/GDP complex activates adenylate cyclase resulting in cAMP.
   - cAMP: Activates protein kinase A - phosphorylates enzymes.
2. Gi: Inhibitory protein
   - activated by noradrenalin, prostaglandins, opiates and many peptides which drecrease cAMP
3. Gq
   - activated by Ach