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

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

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)

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

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)

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.