Pharmacological evidence for system-dependent involvement of protein kinase C isoenzymes in phorbol ester-suppressed gap junctional communication

Several phorbol esters are potent activators of protein kinase C. They down -regulate gap junctional intercellular communication and induce phosphoryla tion of connexin43, but the sensitivity and extent of responses vary much b etween systems. We asked whether the total protein kinase C enzyme activity or the protein kinase C isoenzyme constitution was of importance for such variations. Some fibroblastic culture systems were compared. It was conclud ed that the total protein kinase C enzyme activity did not determine the se nsitivity to phorbol esters. Furthermore, the use of isotype-specific inhib itors of protein kinase C indicated that protein kinase C alpha, delta, and epsilon may be involved to different extents in different fibroblastic sys tems in the response to phorbol esters. (C) 2001 Academic Press.