Lec 4- Drug targets 2, Page 27-35

Question 1

Receptor family :type 1

Answer 1

Ligand-gated ion channels (inotropic receptors)

Question 2

Receptor family: type 2

Answer 2

G-protein-coupled receptors (metabotropic)

Question 3

Receptor family: type 3

Answer 3

Kinase linked receptors (catalytic)

Question 4

Receptor family: type 4

Answer 4

Gene transcription linked receptors (nuclear/ intercellular)

Question 5

How are families grouped together?

Answer 5

According to structure and signal transduction system

Question 6

Ionotropic Receptors

Answer 6

• nACh, GABAa
• Very fast
• causes a conformational change in the receptor which leads to ion channel opening
• may cause increase in channel opening time (nAChR) or an increase in channel conductance (glutamate)

Question 7

G Protein Linked receptors

Answer 7

• mAchR, adrenoceptors
• Fast (seconds)
• causes activation of G-protein -> opening/ closing of an ion channel or the generation of secondary messengers (cAMP/ IP3) -> biological effect

Question 8

Protein kinases

Answer 8

• Enzymes that attach phosphate groups to proteins -> changes in structure and function
  Eg. PKA and PKC
• sometimes 3rd messengers are operated by protein kinase activation

Question 9

Catalytic Receptors

Answer 9

• Tyrosine-kinase and guanylate cyclase linked receptors (takes minutes to days)
• Growth factors, hormones (insulin) and cytokines
• Receptors trigger a kinase cascade
• Some possess intrinsic kinase activity, others associate w kinases on agonist binding

Question 10

How does transduction work?

Answer 10

1. Dimerisation of receptors
2. Autophosphorylation of tyrosine residues
3. Phosphotyrosine residues act as acceptors for the SH2 domain proteins
4. Control of cell function

Question 11

2 important pathways of catalytic receptors

Answer 11

• Ras/Raf/MAP kinase (cell differentiation)

- Jak/Stat (inflammation)

Question 12

Intracellular Receptors

Answer 12

• Slow- acting (hours), long lasting
• Steroid hormone receptors (oestrogen, cortisol, vitamin A etc)
• Often lipid soluble because it needs to penetrate cell membrane
• Bind to highly conserved regions of DNA attached to variable ligand-binding and transcriptional control domains
  => alteration in gene transcription and therefore protein synthesis