1. Tissue response compared to receptor occupation
Is tissue response proportional to receptor occupation?
i.e. does 50% receptor occupation mean that the tissue response will be 50% of the maximum possible response? No!
Max response occurs when only a small number of receptors occupied, maybe as few as 0.1%!!!!
There are a large number of SPARE RECEPTORS

2. Fractional occupancy vs concentration
100 80 60
% receptor occupancy 40 20
100
200
300
400
500
600
700
Concentration agonist (nM)

3. Fractional occupancy vs concentration II
100 80 60
% receptor occupancy
Value known as Kd
related to affinity 40 20
100
200
300
400
500
600
700
Concentration agonist (nM)

4. Kd Kd known as dissociation constant High Kd = LOW affinity
Low Kd = HIGH affinity
using this graph is not accurate
other ways of calculating Kd - see Prof Beech’s lectures on ligand binding
could also use log conc graph

5. Fractional occupancy vs log conc
100 80 Kd
note log scale
need to antilog
% receptor occupancy 60 40 20
-10 -9 -8 -7 -6 -5
Log conc agonist (M)

6. Recommended Reading Tissue Response
Medical Pharmacology at a glance, 5th Ed: Page 10
Pharmacology, 5th Ed: Page 15, Fig 2.8
Basic and Clinical Pharmacology Online Book: Section I, Chapter 2, Relation between drug concentration and response.