ANALYSIS OF EFFECTS OF CORTICOTROPIN, FORSKOLIN AND FLUORIDE ON ACTIVITY OF ADENYLATE-CYCLASE OF BOVINE ADRENAL-CORTEX

A mathematical model relating the activity of adenylate cyclase (AC) w ith concentrations of stimulators, equilibrium dissociation constants, specific activity and efficacies of AC depending on the states of its binding sites has been developed and used for analysis of the data on activation of AC of bovine adrenal cortex plasma membranes presented in (De Forests et al. (1987) FEBS Lett. 216, 107-112). Equilibrium dis sociation constants, x(h) and x(l), corresponding to high- and low-aff inity forskolin-binding sites were estimated to be 0.37 and 17 mu M; t hese constants characterize forskolin's potency more adequately than d oes ED(50), the concentration eliciting half-asymptotic activity of AC . Corticotropin does not affect the affinity of AC for forskolin where as fluoride increases this affinity, thus augmenting forskolin's poten cy. Hormone receptor of adenylate cyclase of bovine adrenal cortex has been suggested to have two or more binding sites for corticotropin. S ome unidentified factor(s) may be responsible for the differences foun d in adenylate cyclase activity in different experiments carried out u nder similar conditions. The model applied for the analysis may be tho ught to be the best means for the moment to relate dose-response depen dencies with what is known or can be hypothesized about the mechanisms underlying activation of adenylate cyclase.