Effects of forskolin on adenylate cyclase activity and amylase secretion in the rat exocrine pancreas.

Abstract

Forskolin stimulated adenylate cyclase activity 55-fold in crude rat pancreatic plasma membranes. Dose-response curves were better fitted by a two-component model with apparent Ka for forskolin of 0.8 microM and 85 microM corresponding, respectively, to 15% and 85% of total activity. Gpp (NH)p alone or the combined presence of GTP plus a hormone (secretin, VIP or CCK-8) potentiated activation through the high affinity forskolin component. These results are in favour of a dual mode of action of forskolin: a high affinity component related to the stimulatory guanine nucleotide-binding regulatory subunit, and a low affinity component more closely related to the catalytic subunit of the enzyme. In dispersed rat pancreatic acini, forskolin increased cyclic AMP levels 26-fold and potentiated the increase induced by secretin, VIP, and CCK-8. It also stimulated the phosphorylation of three particulate proteins (Mr = 21K, 25K and 33K). In terms of secretion, it raised amylase secretion by 60%, a weak effect comparable to that exerted by VIP but much lower than that of secretin or CCK-8. Forskolin did, however, potentiate the secretory effect of CCK-8 (a hormone inducing a redistribution of cellular calcium) while being without influence on the secretory effects of secretin and VIP.