CELLULAR RECEPTORS AND DRUG ACTION

Question 1

What are G protein coupled receptors?

Answer 1

Stimulate effectors to produce intracellular changes

Question 2

What are the 3 G protein subgroups?

Answer 2

Gs, Gi, Gq

Question 3

What is Gs?

Answer 3

Stimulatory stimulates effector

Question 4

What is Gi?

Answer 4

Inhibitory inhibits effector

Question 5

What is Gq?

Answer 5

Doesn’t do anything

Question 6

What do receptors that interact with G proteins include?

Answer 6

Light, hormones, neurotransmitters, prostaglandins

Question 7

What causes the G protein to stimulate an effector?

Answer 7

Binding of a ligand

Question 8

What are the effectors?

Answer 8

1. Ion channels
2. Adenylyl cyclase
3. Phospholipase C (PLC)

Question 9

What are ion channels?

Answer 9

Cardiac muscarinic receptor

Question 10

What is adenylyl cyclase?

Answer 10

• this enzyme makes cAMP from ATP
• cAMP is a 2nd messenger

cAMP signal transduction pathway

Question 11

What is phospholipase C (PLC)?

Answer 11

• PLC acts to cleave PIP
• the cleaved PIP yield IP3 and DAG
  - IP3 and DAG are both 2nd messengers

Phosphatidylinosital signal transduction pathway

Question 12

What is the cardiac atrial muscarinic receptor?

Answer 12

1. Ligand binding at a receptor site leads to stimulation of a G protein
2. G protein stimulation induces opening of an ion channel

Question 13

What happens with the cardiac atrial muscarinic receptor?

Answer 13

• coupled to a G protein that is connected to a K+. Channel
• when acetylcholine binds to the muscarinic receptor, the associated G protein is stimulated
• the G protein in turn activated the K+ channel to open
• K+ leaves the cell, hyper-polarizing the cellular membrane and slowing the heart

Question 14

Gs proteins linked to adenylyl cyclase

Answer 14

• stimulate adenylyl cyclase (the effector)
• adenylyl cyclase converts ATP into cAMP (cyclic amp)
• cAMP is a 2nd messenger that binds to, and activates protein kinases
• protein kinases activate enzymes by adding a phosphate group

Question 15

Gi proteins linked to adenylyl cyclase

Answer 15

• inhibits adenylyl cyclase (the effector)
• activation of Gi leads to a decrease in cAMP since no new cAMP is made

Question 16

What is albuterol/salbutamol?

Answer 16

A bronchodilator, is a specific beta2- adrenergic receptor agonist

• binding to the receptor activates adenylyl cyclase via the Gs protein

Question 17

What happens when there is an increase is cAMP.

Answer 17

• causes the activation of enzymes that sequester Ca+ and inactivate MLCK (myosin light chain kinase)
• decreased levels of Ca+ and MLCK leads to relaxation of the bronchial smooth muscle (can breathe again)

Question 18

What is misoprostol?

Answer 18

A peptic ulcer drug, binds to the Gi linked prostaglandin EP3 receptor
- receptor binding inhibits adenylyl cyclase
- cAMP production decreases
- protein kinases are not activated by cAMP
- enzymes and pumps that help produce stomach no longer activated
- production of stomach acid decreases
- the drug also causes uterine contraction and is CONTRAINDICATED pregnancy

Question 19

Gq linked to phosoholipase C

Answer 19

Activated by Gq proteins
- PLC acts to cleave PIP
- the cleaved PIP yields 2nd messengers
— inositol triohosphate (IP3)
— DAG (diacylglycerol)
- IP3 binds to the sarcoplasmic reticulum and stimulates the release of Ca+ into the cytoplasm
-DAG binds to Ca+ into the cytoplasm
-DAG binds to calcium channels on the cell membrane, facilitating the movement of extra cellular calcium into the cell (entry)
Calcium influx into the cytoplasm (both pathways) produces the biological response

Question 20

Gq linked to phosoholipase C (Ergonovine)

Answer 20

Binds to a Gq protein linked prostaglandin E1 receptors in the uterus and Gq protein linked adrenoceptors in the blood vessels
- receptors binding stimulates PLC to produce IP3 and DAG
- IP3 binds to the sacroplasmic reticulum and induces the release of Ca2+ into the cytoplasm
- induces contraction of the uterus and blood vessels
- can be used clinically to manage postpartum hemorrhage
- monitor pt for dangerous increases in BP