Receptor Lecture 2 – Receptor agonists : inducing a response

Question 1

Ligand

Answer 1

Something that binds (natural ligand, drug, etc.)

Question 2

Agonist

Answer 2

a ligand that binds to and activates a receptor

Question 3

Agonists and Receptors

Answer 3

Agonists are ligands that activate the receptor
Drives the response

E.g. Acetylcholine is the agonist for both Nicotinic ligand-gated ion channels and muscarinic G protein-coupled receptors

Question 4

The concentration response curve

Answer 4

1) Initial low concentrations evoke limited response
Low receptor occupancy, poor response
2) Eventually increasing concentrations evokes increasing response in linear fashion
3) Finally response is maxed out (full receptor occupancy, maximal biological response)

Question 5

The concentration response curve - EMax

Answer 5

Emax - maximum effect produced by an agonist

How effective the agonist is at producing a response

Maximum effect produced by agonist not necessarily the maximum response of biological system

Question 6

The concentration response curve - EC50

Answer 6

EC50 - Concentration of agonist required to elicit 50% of maximal response (Emax)

Useful measure to compare between different agonists in same system

Question 7

Ec 50

Answer 7

is comparing the potency

Higher concentrations of agonist B are required to produce the same response as agonist A

Agonist B is therefore less potent than agonist A

EC50 (Concentration that elicits 50% response - potency)

Question 8

Emax

Answer 8

same E max Both agonists have same efficacy
EMAX (Maximal response of agonist - efficacy)

Question 9

Partial Agonists

Answer 9

Some agonists receptor interactions do not produce a full response in a biological system

Either have limited receptor occupancy (Poor Affinity)
Or can’t effect a full response (Poor Efficacy)

Referred to as a partial agonist

Agonists that produce a full response are full agonists

Question 10

Inverse Agonists

Answer 10

Some biological systems and receptors have a basal level of activity without any agonist present
Termed ‘constitutive activity’
E.g., Heart muscle contraction

This activity can be reduced by certain drugs

These are called Inverse Agonists

Agonist D reduces biological response below basal levels

Agonist C Emax = -50%

Question 11

Biased Agonism

Answer 11

Different agonists can produce different effects through the same receptor

Promote different activation states of receptor – different second messengers – different response

Termed Biased Agonism

lung development
Embryonic lungs respond differently to agonists FGF7 and FGF10

FGF7 induces growthFGF10 promotes airway branching

Both act through same receptor FGFR2