L5 - Receptor Theory

Question 1

Most drugs target proteins such as

Answer 1

Receptors
Enzymes
Transporters
Ion channels

Question 2

What is a receptor?

Answer 2

A proteins whose function it is to recognize and respond to endogenous chemical signals 
Receptors show specificity in the class of drug that they recognize

Question 3

What is a drug target?

Answer 3

Other macromolecules with which drugs interact

Question 4

Receptors are classified by

Answer 4

Structure
Pharmacology
Signalling

Question 5

4 different receptor families

Answer 5

Type 1 – ligand gated ion channels – ionotropic
Type 2 – G-protein coupled receptors – metabotropic
Type 3 – kinase linked receptors
Type 4 – nuclear receptors

Question 6

GPCR structure

Answer 6

7 transmembrane domains
3 intracellular loops linking the transmembrane domains
Amino terminus faces the extracellular environment
Carboxyl terminus faces the intracellular environment
2 binding domains

Question 7

GPCR signalling

Answer 7

Agonists binds to receptor initiating activation of G-protein (alpha, beta, gamma subunits)
Activates a signalling cascade which amplifies the response

Question 8

GPCR effectors

Answer 8

Adenylyl cyclase
Guanylyl cyclase
Phospholipase C

Question 9

Adenylyl cyclase

Answer 9

Enzyme that controls the production of cAMP

Question 10

Phospholipase C

Answer 10

Breaks down phospholipids (PI(4,5)P2) 
Requires Ca for its function 
Two second messengers produced 
•	IP3 - diffuses into the cytosol 
•	DAG - remains in the plasma membrane

Protein kinase A – regulated by cAMP
Protein kinase C – regulated by DAG
- Phosphorylate proteins once activated by 2nd messengers

Question 11

Ion channels

Answer 11

Beta-gamma subunits – regulate the gating of certain ion channels
Alpha subunits – interacts and regulates the activity of the enzymes

Question 12

GPCR examples

Answer 12

Beta 2 adrenoceptors 
Rhodopsin 
Muscarinic receptors 
Opioid receptors 
Dopamine receptors

Question 13

2 types of G protein

Answer 13

Heterotrimeric G-protein (alpha subunit has the GTPase activity)
Monomeric G-protein

Question 14

RTK structure

Answer 14

1 transmembrane domain

Question 15

RTK signalling

Answer 15

Require crosslinking between two RTKs to become active

Once activated they activate a kinase enzyme that phosphorylates tyrosine amino acids

Question 16

RTK effectors

Answer 16

MAP kinase
Phospholipase C gamma
RAS – monomeric G-proteins (then controls MAP kinase)

Question 17

RTK examples

Answer 17

Insulin receptor
Chemokine and cytokine receptors
Growth factor receptors

Question 18

Arrestin

Answer 18

A protein that binds to GPCRs and stops their signalling function – desensitisation of receptors

Question 19

Ligand gated ion channel structure

Answer 19

4 transmembrane domains
1 binding domain - N terminus
Both N and C lie extracellular

Question 20

Kinase linked receptors structure

Answer 20

1 transmembrane domain
N lies extracellular
C lies intracellular

Question 21

Nuclear receptor structure

Answer 21

0 transmembrane domain

Question 22

Activation of Gs

Answer 22

Leads to activation of adenylyl cyclase and guanylyl cyclase

Question 23

Activation of Gq

Answer 23

Leads to activation of Phospholipase C

Question 24

Guanylyl cyclase

Answer 24

Enzyme that controls the production of cGMP

Question 25

Which proteins do PKA and PKC phosphorylate?

Answer 25

Phosphorylate proteins at the Serine and Threonine amino acid residues.