MODULATION OF PROTEIN-KINASE-C AND CAMP-DEPENDENT PROTEIN-KINASE BY DELTA-OPIOID

Modulation of protein kinase C (PKC) and cAMP-dependent protein kinase (PKA) activities by delta-opioid receptor specific agonist [D-Pen(2), D-Pen(5)]-enkephalin (DPDPE) was investigated in neuroblastoma X glio ma hybrid NG 108-15 cells. DPDPE activated PKC in a dose-dependent man ner, with the maximal response at 5 min. The DPDPE-stimulated PKC acti vation could be blocked by naltrindole. The activation of PKC by DPDPE was dependent on Ca2+ and was inhibited by chelerythrine chloride (10 mu M), but not by H89 (1 mu M). Pretreatment of NG 108-15 cells with pertussis toxin (100 ng/ml for 24 h) completely abolished DPDPE-stimul ated PKC activation. In contrast to the result from the acute treatmen t with DPDPE, which had no significant effect on PKA activity, chronic treatment of DPDPE (1 mu M for 24 h) increased PKA activity, but redu ced the basal activity of PKC. These results demonstrated that DPDPE d ifferentially modulated PKC and PKA activities via a receptor-mediated , PTX sensitive pathway. (C) 1997 Academic Press.