W2: Pharm L: Receptors & Membrane Signalling

Question 1

Types of extracellular hormone signals

Answer 1

Endocrine - signalling over a distance through circulation
Paracrine - signalling from nearby cells or tissues (local)
Autocrine - signalling from the same cell via the extracellular space

Question 2

G protein couple receptors - effect following agonist binding

Answer 2

The release of a G-protein whose alpha, or beta-gamma subunits can travel in the membrane to affect other enzymes or channels in the membrane. Activates or inhibits a second messenger system. E.g., adrenoreceptirs or muscarinic receptors.

Question 3

How does a G protein receptor work?

Answer 3

A G protein has an alpha, beta and gamma subunit. They exist naturally with GDP bound to the alpha subunit. When a ligand binds, the G protein phosphorylates itself so it becomes GTP, making it unstable so the alpha subunit dissociates from the beta and gamma. The alpha subunit can now bind to a target protein to have more effects.

Question 4

What are the 4 types of receptor?

Answer 4

G protein couple receptors
Enzyme linked receptors
Receptors than regulate gene transcription
Channel-linked receptors

Question 5

What is drug affinity?

Answer 5

The affinity of a drug for its receptors is a measure of how well it binds to a chemically sensitive site or receptor. Kd. This is equal to the concentration at which, at equilibrium, half the receptors will be bound with the ligand.

Question 6

What does binding of a ligand do to a receptor?

Answer 6

Binding of a ligand induces change in the structure of the receptor which changes it’s function, leading to a signalling cascade. Each of the molecules that changes downstream of the receptor is called a second messenger.

Question 7

Channel linked receptors (ligand gated ion channels) - effect following agonist binding

Answer 7

An ion channel will open

Question 8

Channel linked receptors (ligand gated ion channels) - common consequences

Answer 8

The membrane potential changes and intracellular ion concentrations change

Question 9

Channel linked receptors (ligand gated ion channels) - examples

Answer 9

Nicotinic acetylcholine receptor

Question 10

G-protein couple receptors - common consequences

Answer 10

Activation or inhibition of a second messenger system such as those involving cAMP.

Question 11

G-protein coupled receptors - examples

Answer 11

Adrenoceptors (all), muscarinic receptors (for ACh)

Question 12

What is the benefit of g-proteins being small?

Answer 12

Smaller than proteins, so can diffuse in the cytoplasm and move relatively quickly.

Question 13

Enzyme-linked receptors - effect following agonist binding

Answer 13

Activates the intrinsic enzyme which is typically either a tyrosine kinase or a guanylyl cyclase.

Question 14

Enzyme linked receptors - common consequences

Answer 14

Autophosphorylation of the proteins (for kinases), which changes their ability to bind with other signalling molecules, or an increase in the concentration of a second messenger.

Question 15

Enzyme linked receptors - examples

Answer 15

Receptors for growth factors and insulin, ANF

Question 16

Receptors that regulate gene transcription - effect following agonist binding

Answer 16

Binding to the cytoplasmic receptor leads to the receptors moving into the nucleus.

Question 17

Receptors that regulate gene transcription - common consequences

Answer 17

A change in gene expression and hence protein transcription/translation

Question 18

Receptors that regulate gene transcription - examples

Answer 18

Steroid receptors (e.g., aldosterone receptors)

Question 19

Drug receptor complex

Answer 19

D + R <-> DR