[CA2-KINASE-C IN VASOPRESSIN-INDUCED PROSTACYCLIN AND ANP RELEASE IN RAT CARDIOMYOCYTES(](I) AND PROTEIN)

Exposure of cultured, spontaneously beating rat cardiomyocytes to argi nine vasopressin (AVP) led to marked increases in the release of prost acyclin (PGI(2)) and atrial natriuretic peptide (ANP). These responses were accompanied by a rapid, transient rise of cytosolic free Ca2+ co ncentration ([Ca2+](i)) and of membranous protein kinase C (PKC) activ ity. Ca2+ influx and PKC activity appeared to play important but disti nct roles in AVP-induced cellular responses, insofar as only AVP-induc ed ANP secretion was abolished by the Ca2+ channel antagonist nifedipi ne, whereas both AVP-induced PGI(2) production and ANP release were ab olished by the PKC inhibitors staurosporine and CGP-41251. The AVP-ind uced increase in [Ca2+](i) could also be mimicked with the vasopressin (V-1-subtype) agonist Octapressin, but not with the V-2-agonist 1-des amino-8-D-arginine vasopressin, and was fully abolished by the V-1-ant agonist [d(CH2)(5)Tyr(Me)]AVP, but not by d(CH2)(5)-D-Leu-VAVP (V-1-/V -2-antagonist). These results indicate that V-1-vasopressinergic recep tors mediate AVP-induced PGI(2) production and ANP secretion in rat ca rdiomyocytes and that, whereas both Ca2+ influx and PKC activation are required for AVP-induced ANP secretion, AVP-induced PGI(2) formation is mainly regulated by PKC.