PHORBOL ESTERS INCREASE ADENYLATE-CYCLASE ACTIVITY AND STABILITY IN PITUITARY MEMBRANES

In this report, we demonstrate that calcium and phorbol esters enhance cAMP production in GH4C1 cell homogenates. The mechanism for this is a reduction in the rate of decay of adenylate cyclase activity over the course of the assay. Purified protein kinase C can reconstitute calcium- and phorbol ester-dependent adenylate cyclase. Phorbol ester-activated protein kinase C increases both the initial rate of cAMP synthesis and reduces the time-dependent decay of adenylate cyclase activity in membrane preparations. The rate of cAMP production is fit to an equation derived from a model which assumes that adenylate cyclase initially exists in a high activity state which decays exponentially into a low activity state. We suggest that protein kianse C can both prevent the decay of the high activity state and convert the low activity state into the high activity state.