SL12100

LECTURE 15: WHAT IS A RECEPTOR? TYPES + FUNCTION

1. Key Ideas:
i) Different types of drug targets. - Kinase linked receptor.
- Receptors, ion channels, enzymes + - Nuclear receptors.
transporters. iv) Describe how each receptor type is
ii) How cells recognize and respond to activated.
signals. - Channel opening.
- Signal -> Action -> Response. - Activation of G-protein.
iii) Different types of receptors. - Activation of kinase enzyme
- Ligand-gated ion channel. (phosphorylation).
- G-couples receptor (GPCR). - Movement to nucleus (gene
expression).
2. What is pharmacology?
- The science of drugs and how they act in a biological system.

3. Receptor pharmacology:
- Receptor = proteins, usually on the surface of a cell which receives and transduces signals.
- Ligand = something that binds.
- Second messenger = relay signal from receptor to effector.
- Signal transduction = sequence of second messengers that elicit a biological response.
 4. Basics of ligand-receptor interactions:
1. Ligand binds to receptor.
2. Causes conformational change of receptor protein.
3. Results in cellular effect.
i) Opening of channel.
ii) Activation of linked enzyme.
iii) Recruitment of effector protein.
iv) Intracellular response.

5. Receptors overview:

6. Ligand-gated ion channels:

- Distinct from other ion channels.
- Channel opens in response to ligand binding.
- Allows movement of channel specific ions.
- Eg. acetylcholine and nicotinic acetylcholine receptors.

i) Electrical impulses travel down the pre-synaptic neuron.

ii) Triggers release of acetylcholine.
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 iii) Acetylcholine acts on nAChRs on post synaptic neuron.
iv) Opens channel, allows sodium ion entry, triggers electrical impulse.

7. G protein coupled receptors (GPCRs):

- 7 transmembrane domains.
- Coupled G protein.
- Ligand binding activated G protein which interacts with effector.
- Different GPCRs couples to different G proteins illicit different effects.

- Eg. muscarinic receptor and smooth muscle contraction.

i) Muscarinic M3 GPCRs present on smooth intestinal muscle.

ii) Activation causes contraction (peristalsis).
iii) Antimuscarinics are used for IBS.

8. Kinase linked receptors:

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 - Receptor in two halves in the membrane (monomer).
- Ligand-receptor enhancement brings two receptor proteins together (dimer).
- This activates kinase activity of receptor.
- Initiates downstream cascade and biological response.

- Kinase = second messenger, enzyme, phosphorlates target.

- Uses ATP to add phosphate group onto target.
- Different kinases act on different targets.
- Acts as a switch = turn on/off + allows other second messengers to bind.
- Eg. EGFR and lung cancer.
i) EFGR (type of kinase linked receptor) promotes cell growth.
ii) Some lung cance expresses more EGFR proteins = more growth.
iii) These cancers susceptible to frugs that target EFGR.

9. Nuclear receptor:
- Not associated with cell membrane.
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 - Ligand enters cell + binds to receptor in cytoplasm.
- Ligand-receptor complex then moves into the nucleus.
- Acts on gene expression.

- Eg. oestrogen receptor and breast cancer.

i) Oestrogen receptor = hormone nuclear receptor.
ii) Important for sexual maturation + gestation.
iii) Some types of breast cancer expresses more oestrogen receptors = more growth.
iv) Susceptible to targeted therapy (tamoxifen).