MO24 Receptors As Drug Targets 2

Question 1

What are the 4 types of receptors?

Answer 1

1. ligand gated ion channels
2. GPCR
3. Kinase-linked receptors
4. Nuclear receptors

Question 2

How do receptors work as drug targets?

Answer 2

Receptors communicate between cells via the nervous system (CNS AND AN). An electric pulse is sent along neurons which leads to a chemical messenger (neurotransmitters and circulating hormones) being released. These then bind and interact with a specific receptor. Binding can trigger a cascade of events such as activating ion channels, activating/inactivating intracellular components and causing a biological response.

Question 3

Where are receptors usually located?

Answer 3

In the membrane, they tend to span the membrane of a cell

Question 4

What are the properties of ionotropic receptors?

Answer 4

• fast neurotransmission (milliseconds)
• there is a ligand binding site, usually extra cellular
• the structure is multiple membrane spanning subunits surrounding a pore
• a neurotransmitter will be released into the synapse which will bind to the receptor. This causes a change in shape (eg. A channel to open) which has an effect on the cell (eg. Na+ ions enter the cell ands change the polarity.

Question 5

What are the properties of a G protein coupled receptor

Answer 5

• membrane receptors coupled to intracellular effector systems via G-proteins
• 7 membrane spanning helices
• largest family of receptors
• receptors for many hormones and slow transmitters
• ligand binding induces a signal via a conformational change. The intracellular loop interacts with G proteins. G proteins have 3 subunits, alpha beta and gamma. alpha has GTPase activity which turns GTP->GDP. The signal leads to action of an enzyme or ion channel via second messengers.

Question 6

What are the properties of a kinase-linked receptor?

Answer 6

• an extra cellular ligand- binding domain linked by a transmembrane helix to an intracellular domain (which is often enzymatic)
• signal transduction: 1. Ligand binds extracellularly 2. Receptor dimerisation occurs when the agonist binds which leads to 2 receptors coupling together 3. ATP leads to auto phosphorylation of tyrosine (amino acid) residues via kinases. The tyrosine kinases in each receptor phosphorylate the other member of the dimer. 4. intracellular (relay) proteins bind to the phosphotyrosines allowing control of cell functions (cellular response) eg cell growth and differentiation

Question 7

What are the properties of nuclear receptors?

Answer 7

• regulate gene transcription
• intracellular receptor (not on the membrane)
• mode of action: 1. ligand diffuses into cell 2. Ligand binds to nuclear receptor 3. Liganded receptors dimerise and translocate to the nucleus 4. Activate (or repress) genes by binding to response elements 5. Binds to DNA and initiates transcription