Lecture 16: G-protein coupled receptors as drug targets

Question 1

What are G protein-coupled receptors?

Describe what happens when a G protein is activated

Answer 1

• Is a receptor found in the membrane that is coupled/connected to a G protein
• Once an agonist binds to the receptor, the G protein becomes activated
• This activated G protein in turn can increase or decrease the activity of an enzyme
• Change in enzyme activity will change the amount of 2nd messengers in the cells which alters the physiological biochemistry of the cell

Question 2

What are the reaction responses for:

• ligand/voltage gated receptors
• nuclear receptors
• G protein-coupled receptors

Answer 2

ligand/voltage = milliseconds
nuclear = hours - days
G protein = seconds

Question 3

What do second messengers do?

Answer 3

The amount of second messenger changes the biochemistry/physiology of the cells e.g cAMP

• The type of second messenger is dependant of the G protein
• drug binds- activates G protein - decrease/increase activity of enzyme - changes the amount of 2nd messengers - alters the physiology biochemistry of the cells

Question 4

How does an antagonist block a G protein receptor ?

Answer 4

An antagonist is a drug which binds to the receptor but does NOT induce an effect - does not change shape - it prevents the agonist from binding - blocks the effects from the agonist

• therefore G protein cannot be activated
• disease state can be due to too much receptor activation so an antagonist is used to block the receptors

Question 5

How do antipsychotic treatment block psychosis?

Psychosis = inability to perceive reality - delusions and hallucinations

What is the problem with anti-psychotics?

Answer 5

In psychosis you get a high level of dopamine receptor activation so:
- antipsychotics are used to block the dopamine at the dopamine receptor activation
- Antipsychotics stop the excess dopamine activating the dopamine receptor
- Act as an antagonist of dopamine receptors
= Can induce parkinson’s disease like movements

Question 6

How do the levels of dopamine differ btw normal people and people with parkinson’s disease

Answer 6

normal people = normal levels of dopamine
- no loss of dopamine neurons
- normal dopamine receptor activation
parkinson’s disease
- loss of dopamine neurons
- no dopamine & no dopamine receptor activation
- unchecked signally messenger

Question 7

What is an example of an agonist?

Answer 7

A drug that binds to the receptor and induces an effect

• Dopamine is a neurotransmitter which activated dopamine receptors (a G coupled receptor)
• Low levels of dopamine receptor activation results in parkinson’s disease

Question 8

What is an example of antagonist ?

Answer 8

Antipsychotics

- act as antagonist at dopamine receptors