Effects of forskolin on adenylate cyclase activity and amylase secretion in the rat exocrine pancreas.
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.
J P
JP
Dehaye
M
M
Gillard
P
P
Poloczek
M
M
Stievenart
J
J
Winand
J
J
Christophe
D000067956:Adenylyl Cyclase Inhibitors; D000681:Amylases / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D005576:Colforsin; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006150:Guanine Nucleotides / Q000378:metabolism; D066298:In Vitro Techniques; D008861:Microsomes / Q000201:enzymology; D010179:Pancreas / Q000201:enzymology* / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D012633:Secretin / Q000494:pharmacology; D012844:Sincalide / Q000494:pharmacology; D013997:Time Factors; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D004224:Diterpenes; D006150:Guanine Nucleotides; D012633:Secretin; D005576:Colforsin; D014660:Vasoactive Intestinal Peptide; D000681:Amylases; D012844:Sincalide