Receptors

Question 1

Partial agonist?

Answer 1

Binds and activates receptor. Partial efficacy compared to a full agonist even at maximal receptor occupancy

Question 2

Inverse agonist?

Answer 2

Bonds to same receptor site as agonist.
Inhibits constitutive activity of receptor.
Exerts opposite response to agonist.

Question 3

Prerequisite for inverse agonist?

Answer 3

The receptor must have a constitutive activity in the absence of an agonist

Question 4

Potency of agonist?

Answer 4

Half the maximal effective concentration of agonist- EC(50)

Question 5

Relationship of EC(50) and potency?

Answer 5

The smaller the EC(50) the more potent the agonist

Question 6

List the 4 receptor types

Answer 6

LGIC
GPCR
single transmembrane receptor
Intercellular receptor

Question 7

How is the margin of safety of a drug evaluated?

Answer 7

By the therapeutic index.
TC(50)/EC(50
The bigger the better

Question 8

Difference between drug specificity and selectivity?

Answer 8

Drug selectivity:
Drug has greater affinity for one receptor over another.
Other receptor still has some binding and activity.

Drug specificity:
No increase in drug can activate the other receptor

Question 9

What types of LGICs are there?

Answer 9

Pentameric
Tetrameric
Trimeric

Question 10

Give examples of pentameric LGICs.

Answer 10

Nicotinic ACh
GABA (A)
Glycine
Serotonin (3)

Question 11

Give an example of a tetrameric LGIC

Answer 11

Glutamate

Question 12

Give an example of a Trimeric LGIC

Answer 12

ATP

Question 13

How many transmembrane helices are in a GPCR?

Answer 13

7

Question 14

Where is the N terminus and C terminus positioned on a GPCR?

Answer 14

N terminus is extracellular

C terminus is intercellular

Question 15

How much time does it take to activate a LGIC

Answer 15

Less than one millisecond

Question 16

How much time does it take to activate a GPCR?

Answer 16

Seconds to minutes

Question 17

4 types of G proteins

Answer 17

S
I
O
Q

Question 18

What does Gs do?

Answer 18

Stimulates AC

Question 19

What does Gi do?

Answer 19

Inhibits AC

Question 20

What does Go do?

Answer 20

Stimulate PLC-beta

Question 21

What does Gq do?

Answer 21

Stimulate PLC-beta

Question 22

What’s a full agonist?

Answer 22

A ligand which binds and activates a receptor, producing maximal efficacy at that receptor

Question 23

What are the key events in tyrosine kinase activation?

Answer 23

Ligand binds to extracellular receptor domain
2 receptors dimerise
A conformational change of the intracellular kinase domains renders the active sites available for autophosphorylation by ATP

Question 24

Where in the cell are steroid receptors found?

Answer 24

In the cytosol

Question 25

What macromolecule do steroids activate?

Answer 25

DNA

Question 26

Where is the dose response curve of a ligand more potent than another?

Answer 26

Closer to zero on the x axis

Question 27

What’s different about the dose response curve of a ligand with a greater efficacy than another?

Answer 27

It is longer on the y axis

Question 28

How does the Castillo & Katz mechanism explain how a partial agonist operates?

Answer 28

It shows that a ligand can be bound to a receptor without it activating it.

Question 29

If the efficacy at a receptor is 1, what is the efficacy of an antagonist at that receptor?

Answer 29

The efficacy of an antagonist is always 0.

Question 30

What is the pA(2) of an antagonist?

Answer 30

It’s the antagonist potency

=-logK(b) for a competitive antagonist

Question 31

How is the pA(2) evaluated?

Answer 31

Does not depend on K(A)
Increases linearly with x(B)
Slope of plot of (r(A)-1) against x(B) is 1/K(B)
Relationships independent of agonist characteristics
Should be the same for all agonists on the same population of receptors