Receptor theory III

Question 1

How is the response of a drug measured?

Answer 1

In a bioassay

• Apply different concentrations of drugs and measure the outcome

Question 2

What does a response curve look like?

Answer 2

• Similar to an affinity curve

- Sigmoidal shape which reaches a maximum

Question 3

What is measured in response curves and what is this?

Answer 3

Ec50

The concentration of the drug which gives 50% of the maximal response

Question 4

What is the difference between Ec50 and Kd for a FULL AGONIST?

Answer 4

• Ec50 is a measure of the concentration of the drug which gives 50% the maximal response
• In a concentration- response curve
• Kd is the concentration of drug at which 50% of the receptors are occupied
• In a concentration- binding curve (Langmuir plot)

Question 5

What is the relationship between Ec50 and Kd of a FULL AGONIST?

Answer 5

• Ec50 is shifted to the left of Kd for that particular concentration (NOT EQUAL)
• NOT 50% occupancy with 50% response!!!
• Less occupancy needed for more response
• Shifted to the left due to amplification through secondary messengers
• Smaller concentration to produce 50% response

Question 6

What is a receptor reserve and why is this important?

Answer 6

Spare receptors in a tissue, which are more than is needed to produce a maximum response

Can afford to lose receptors in tissues without impacting the function of the tissues

If increase partial agonist concentration - can bind to the receptors in the receptor reserve and produce a closer o maximum response

If increase full agonist concentration - no change in the maximum response

Question 7

How does the response curve not match the binding curve and why is this?

Answer 7

The response curve is shifted to the left of the binding curve (Ec50 is lower than KD)

Because there is AMPLIFICATION in the system through secondary messengers

Question 8

What is the maximum response determined by?

Answer 8

Efficacy

Question 9

What does the dose-response curve location on the graph depend upon? (left to right)

Answer 9

The POTENCY of the drug, which is dependant on:

• Affinity
• Efficacy
• Receptor reserve

Question 10

What does the hill equation describe?

Answer 10

The relationship between the SIZE of the response and the CONCENTRATION of the agonist added

Question 11

What does the hill coefficient tell you and what is this related to?

Answer 11

How steep the slope is

Related to:
How many molecules of agonist is needed to bind to a receptor to generate a response

Question 12

How many molecules of agonist is needed to bind to a receptor to generate a response and what is the exception?

Answer 12

Normally 1

But can be 2, for example, for ligand gates ion channels

Question 13

What can be used to predict the response for any concentration of drug?

Answer 13

The hill equation

Question 14

Why can’t a low Ec50 be used to conclude that that drug has the highest affinity for a certain receptor?

Answer 14

• Ec50 determines the potency
• The lower the Ec50, the higher the potency

But potency is determined by:

• Affinity
• Efficacy
• Spare receptors

Question 15

What does increasing the spare receptors in a tissue do to the response curve and why?

Answer 15

• Shifts it to the left
• Higher the probability of the receptor to encounter a ligand
• Increase potency

Question 16

What can drawing up many dose-response curves show when testing them in different tissues (with the same ligand/receptor pair)

WHY this and not the other factors that are determined by potency?

Answer 16

Which tissue has the most spare receptors

Cant be affinity as it is the ‘same receptor-ligand pair’ - Kd (and affinity) is CONSTANT in this case

Question 17

What are partial agonists?

Answer 17

Agonists which cannot produce the maximum response

Question 18

What do agonists with different efficacies produce?

Answer 18

Different maximal responses

Question 19

Does a partial agonist have a higher or lower efficacy than a full agonist?

Answer 19

A lower efficacy - produces less than maximum response

Question 20

What is the relationship between efficacy and affinity?

Answer 20

No relationship

An agonist with a high affinity can have a low efficacy

Question 21

What is the relationship between EC50 and Kd for a partial agonist and why?

Answer 21

They are equal

Why:
- For a partial agonist to make a max response, need 100% occupancy

• So, conc of drug producing 50% of response is the same as 50% occupancy

Question 22

What is the ‘potency’ of a drug?

Answer 22

The concentration of a drug needed to produce a specific intensity of response

Question 23

Describe the dose-response curve

Answer 23

Sigmoidal graph

Concentration of AGONIST vs % of maximum response

Question 24

Which graph is the dose-response curve similar to?

Answer 24

Affinity (langmuir)

Question 25

What can the dose-response curve be used to work out?

Answer 25

EC50 (concentration of agonist where there is 50% of maximum response)

Question 26

Why are antagonists not referred to as ‘full’ or ‘partial’

Answer 26

Because is refers to the level of response in the tissue (is it maximal or not)

Antagonists do not cause a response in the tissue

Question 27

Does potency refer to antagonists?

Why?

Answer 27

No - they do not produce a response in the tissue