Activation of protein kinase C is not an absolute requirement for amylase release from permeabilized rat pancreatic acini.
The effect of protein kinase C (PKC) on amylase discharge from streptolysin-O-permeabilized rat pancreatic acini was investigated. Addition of phorbol 12-myristate 13-acetate (PMA) to permeabilized cells potentiated Ca(2+)-stimulated release, but had no effect on discharge at non-stimulatory Ca2+ concentrations. PMA markedly shifted the Ca(2+)-concentration-dependence of amylase discharge to the left, by enhancing the time over which the permeabilized cells release. This effect was inhibited by both staurosporine and PKC-19-31-amide peptide inhibitor, indicating that the effect of PMA was due to its action on PKC. Staurosporine also partially inhibited amylase release at the optimal concentration of Ca2+; this effect was not replicated by the more specific PKC-19-31-amide peptide inhibitor and may be due to an effect on another second-messenger system. PKC appears to be an important modulator of release in pancreatic acini, but its activation is not an absolute requirement for Ca(2+)-dependent amylase discharge.
O'Sullivan
A J
AJ
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510.
Jamieson
J D
JD
D000470:Alkaloids / Q000494:pharmacology; D000681:Amylases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002413:Cations, Divalent; D000242:Cyclic AMP / Q000494:pharmacology; D004789:Enzyme Activation; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology*; D010455:Peptides / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D002413:Cations, Divalent; D010455:Peptides; C061479:protein kinase inhibitor peptide; D000242:Cyclic AMP; D011493:Protein Kinase C; D000681:Amylases; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium