Inhibition of forskolin activated adenylate cyclase in hamster adipocyte membranes with prostaglandin E1 and clonidine.

Abstract

The diterpene forskolin has been shown by Seamon et al (Proc. Natl. Acad. Sci., USA, 78: 3363-3367, 1981) to elicit a large increase in adenylate cyclase activity and to permit further activation by GTP, GDP, sodium fluoride and hormones. The present communication documents forskolin activation of adenylate cyclase activity in hamster adipocyte membrane preparations and shows that the forskolin activated enzyme remains susceptible to inhibition by prostaglandin E1 and clonidine. Moreover, the presence of forskolin, while causing stimulation of adenylate cyclase activity does not appear to prevent the interactions of sodium chloride and GTP with the enzyme. Thus, sodium chloride increased both basal and forskolin stimulated adenylate cyclase activity while GTP decreased activities of the sodium chloride and forskolin activated enzymes. Attenuation of adenylate cyclase activity with clonidine and prostaglandin E1 was detected in the presence of forskolin and GTP and sodium chloride were required. The concentration of GTP required to decrease adenylate cyclase activity and to allow attenuation of the enzyme activity by prostaglandin E1 was not altered by the addition of forskolin.