Methods for analyzing and interpreting cooperativity in dose-response curves—II. Partial agonists acting on muscarinic receptors in smooth muscle

Abstract

1. 1. Dose-response curves for eight muscarinic agonists contracting guinea pig ileum were transformed into Hanes-Woolf plots and Hill plots respectively. 2. 2. Hill plots for three full agonists were linear with slopes of 1.6, illustrating positive homotropic cooperativity involving two or more agonist binding sites. 3. 3. Five partial agonists gave curved Hill plots with Hill coefficients of 1.2–1.7 at low agonist concentration and Hill coefficients of 0.3–0.5 at high agonist concentrations. 4. 4. Hanes-Woolf transformations were used to delineate the transition from positive to negative cooperativity and to assist in the interpolation of Hill plots. 5. 5. The results show that all of the agonists studied induce positive cooperativity, and that the difference between full agonists and partial agonists results from the ability of the latter to induce pronounced negative cooperativity at higher concentrations.