Drug Targets

Question 1

Give as many examples of ligand gated ion channels

Answer 1

1st family

• GABAA
• Muscle and nicotinic acetylcholine receptors
• neuronal nAChR
• Inhibitory glycine receptor
• serotonin type 3 receptor

2nd family
- Ionotropic glutamate receptors

Question 2

How many subunits does the muscle nicotinic receptor have? what types of subunits are present.

Answer 2

5 subunits in total
2 alpha
one beta 
one delta 
and one epsilon 

in foetal muscle there is a gamma subunit instead of epsilon

Question 3

in the muscle nicotinic receptor how many transmembrane domains are there and what is each of the uses

Answer 3

4 TM domains

• 2nd domain forms lining of ion channel
• agonist binding site found at N-terminus
• Large loop between TM3 and TM4 which interacts with cytoskeleton and is target for relegatory proteins

Question 4

Give examples of voltage gates ion channels

Answer 4

K+
Ca2+
Na+

Question 5

structure of Na+ and Ca2+ channels

Answer 5

large Alpha and beta subunits
beta gives the channel certain properties
- alpha has 4 pseudosubunits with 6 TM domains
- dipping domain between TM5 and 6 (froms lining)
- TM4 is charges and acts as voltage sensor

Question 6

outline basic NHR mechanism

Answer 6

1. steriod is lipid souble so passes through membrane.
2. binds to glucocortiod receptor which dissociates fromm its heat shock protein.
3. 2 nuclear hormone receptors dimerize and enters nucleus via a pore. undimerized nuclear hormone receptors also enter.

Question 7

Transactivation

Answer 7

dimerized NHR to DNA at HRE site and recruits activation protein with RNA polymerase to activate synthesis.

Question 8

Transrepresssion

Answer 8

undimerized NHR bind to transcription factor and inhibits it.

Question 9

Structure of GPCR

Answer 9

• 7 TM domains - with NH2 terminus outside cell
• bind to most known neurotransmitters
  G-protein binding domain lies between TM5 and TM6 in form of a loop.

Question 10

Gs mechanism

Answer 10

• cAMP is secondary messenger
• Switches protein kinase to active
• phosphorylates protein to regulate activity

Question 11

Gi mechanism

Answer 11

• inhibits cAMP therefor lowers protein kinase activity

Question 12

Gq mechanism

Answer 12

• Activates PLC
• that then splits PIP2 to DAG and IP3
• DAG actiavtes protein kinase C
• IP3 binds the ER to release Ca2+ and enchance protein kinase

Question 13

G-protein activation cycle

Answer 13

-G-protein has GDP bound
- agonist binds to GPCR and Gprotein replaces GDP with GTP
-splits into two parts
1. alpha subunit it GTP attached
2. beta and gamma subunits
alpha is a GTPase so turns GTP ing GDP

Question 14

Nuclear hormone receptor agonists

Answer 14

• Sex hormones
• Thyroid hormones
• Coricosteroids
• Vitamin D
• Retanic acid