GPCRs and Intracellular Signalling

Question 1

What are different ligands acting at adrenoreceptor?

Answer 1

Endogenous ligand

• Noradrenaline
• Adrenaline

Exogenous/synthetic ligands

• Isoprenaline
• Salbutamol
• Propranolol

Pg 4

Question 2

What are agonist and what are some example of them?

Answer 2

Bind to receptors and activate it (leading to intracellular signal transduction events)

1. Anti-asthma: B2 adrenoreceptor agonist (salbutamol and salmeterol).
   - These drugs are used in asthma to cause relaxation of the airways.
2. Analgesia/anaesthesia: U-opioid receptor agonist (morphine and fentanyl).

Question 3

What are antagonist and what are examples of them?

Answer 3

Bind to receptors (have high affinity to the receptor),but do not activate it. (Blocks the effect of the agonist at the receptor)

1. Cardiovascular (hypertension): B adrenoceptor antagonist (propranolol, atenolol)
2. Neuroleptic (anti-schizophrenic):D2 dopamine receptor antagonists (Haloperidol, sulpiride)

Question 4

What is the basic structure of the GPCRs?

Answer 4

• Single polypeptide chain
• 7 transmembrane (7TM) spanning regions
• Extracellular N-terminal
• Intracellular C-terminal

Question 5

What do different GPCRs respond to?

Answer 5

• Ions
• Neurotransmitters (acetylcholine and glutamate)
• Peptide and non-peptide hormone (glucogaon and adrenaline)
• Large glycoproteins (thyroid-stimulating hormone)

Question 6

What does binding of a ligand to the GPCR cause?

Answer 6

Causes a conformational change which allows the active GPCR to bind to a second protein called a G protein

Question 7

What enzyme converts GTP to GDP?

Answer 7

GTPase

Question 8

Where does the process at which the alpha and beta/gamma subunit dissociate occur?

Answer 8

• In the inner surface of the plasma membrane, this is because the alpha and beta/gamma subunit contain lipid modification.
• Meaning they are always associated with the plasma membrane.

Question 9

What does the alpha subunit contain?

Answer 9

• GTPase activity
• This is why the process of alpha activating effector and the beta/gamma activating effector is last a short period of time.

Question 10

What leads to termination of the G-protein signalling?

Answer 10

• The α-GTP and/or βγ interaction with effectors lasts until the α subunit GTPase activity hydrolyses GTP back to GDP.
• α-GDP and βγ subunits then reform an inactive heterotrimeric complex. As the alpha GDP regain its affinity for the beta/gamma subunit.