Modulation of Ca 2+-dependent anion secretion by protein kinase C in normal and cystic fibrosis pancreatic duct cells

Abstract

The study investigated the role of protein kinase C (PKC) in the modulation of agonist-induced Ca 2+-dependent anion secretion by pancreatic duct cells. The short-circuit current ( I SC) technique was used to examine the effect of PKC activation and inhibition on subsequent ATP, angiotensin II and ionomycin-activated anion secretion by normal (CAPAN-1) and cystic fibrosis (CFPAC-1) pancreatic duct cells. The I SC responses induced by the Ca 2+-mobilizing agents, which had been previously shown to be attributed to anion secretion, were enhanced in both CAPAN-1 and CFPAC-1 cells by PKC inhibitors, staurosporine, calphostin C or chelerythrine. On the contrary, a PKC activator, phorbol 12-myristate 13-acetate (PMA), was found to suppress the agonist-induced I SC in CFPAC-1 cells and the ionomycin-induced I SC in CAPAN-1 cells. An inactive form of PMA, 4α d-phorbol 12,13-didecanote (4αD), was found to exert insignificant effect on the agonist-induced I SC, indicating a specific effect of PMA. Our data suggest a role of PKC in modulating agonist-induced Ca 2+-dependent anion secretion by pancreatic duct cells. Therapeutic strategy to augment Ca 2+-activated anion secretion by cystic fibrosis pancreatic duct cells may be achieved by inhibition or down-regulation of PKC.