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) with 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 Foresta et al. (1987) FEBS Lett. 216, 107-112). Equilibrium dissociation constants. chi h and chi l, corresponding to high- and low-affinity forskolin-binding sites were estimated to be 0.37 and 17 microM: these constants characterize forskolin's potency more adequately than does ED50, the concentration eliciting half-asymptotic activity of AC. Corticotropin does not affect the affinity of AC for forskolin whereas fluoride increases this affinity, thus augmenting forskolin's potency. Hormone receptor of adenylate cyclase of bovine adrenal cortex has been suggested to have two or more binding sites for corticotropin. Some unidentified factor(s) may be responsible for the differences found in adenylate cyclase activity in different experiments carried out under similar conditions. The model applied for the analysis may be thought to be the best means for the moment to relate dose-response dependencies with what is known or can be hypothesized about the mechanisms underlying activation of adenylate cyclase.