Receptor Lecture 1 – What is a receptor: types and function

Question 1

Drug Targets

Answer 1

Four main protein targets for drug action

Receptors

Ion Channels

Enzymes

Transporters

Question 2

Basics of ligand-receptor interactions

Answer 2

Ligand binds to receptor
Causes conformational change of receptor protein
Results in cellular effect
Opening of channel
Activation of linked enzyme
Recruitment of effector protein
Intracellular transport
Signal – Action – Response

Question 3

Receptors

Answer 3

Four main families of receptor
Ligand-Gated Ion Channels
G Protein-Coupled Receptors
Kinase-linked Receptors
Nuclear Receptors

Question 4

Ligand-Gated Ion Channels

Answer 4

Distinct from other ion channels (e.g. voltage-gated ion channels)
Channel opens in response to ligand binding
Allows movement of channel-specific ions
Example:
Acetylcholine and Nicotinic acetylcholine receptors

Electrical impulse travels down pre-synaptic neuron
Triggers release of acetylcholine
Acetlycholine acts on nAChRs on post-synaptic neuron
Opens channel, allows sodium ion entry, triggers impulse

Question 5

G Protein-Coupled Receptors (GPCRs)

Answer 5

Receptor with 7 transmembrane domains
Coupled to G protein
Ligand binding activates G protein which interacts with effector
Different GPCRs coupled to different G proteins
Elicit different effects

Muscarinic M3 GPCRs present on intestinal smooth muscle
Activation causes contraction – peristalsis
Antimuscarinics used for irritable bowel syndrome

Question 6

Kinase-Linked Receptors

Answer 6

Receptor in two halves in the membrane (Monomer)

Ligand-receptor engagement brings two receptor proteins together (Dimer)

This activates kinase activity of receptor

Initiates downstream cascade and biological response

kinase
Second messenger
Enzyme – phosphorylates target
Uses adenosine triphosphate (ATP) to add a phosphate group onto target
Different kinases act on different targets
Acts as switch
Turns target on/off
Allows other second messengers to bind

Epidermal growth factor receptor Type of kinase-linked receptor
Receptor Tyrosine Kinase family

EGFR can promote cell growth

Some types of lung cancer express many more EGFR proteins = more growth
These cancers susceptible to drugs that target EGFR

Question 7

Nuclear Receptor

Answer 7

Receptor not associated with cell membrane
Ligand enters cell and binds to receptor in cytoplasm
Ligand-receptor complex moves into nucleus
Acts on gene expression

Oestrogen receptor - hormone nuclear receptor
Important for sexual maturation, gestation

Some types of breast cancer express many more oestrogen receptors = more growth

Susceptible to targeted therapy - Tamoxifen