INHIBITION AND DOWN-REGULATION OF PROTEIN-KINASE-C IN CULTURED ATRIALMYOCYTES - EFFECTS ON DISTRIBUTION OF SPECIFIC GRANULES AND SECRETIONOF ATRIAL-NATRIURETIC-PEPTIDE

Primary cultures of neonatal rat atrial myocytes were subjected to dow n-regulation of protein kinase C (PKC) and to inhibition of PKC activi ty. The effects on secretion of atrial natriuretic peptide (ANP), and the intracellular distribution of ANP-containing specific granules and their association to microtubules, were investigated. Treating the cu ltures with inhibitors of PKC, staurosporine or H7, a translocation of ANP-containing specific granules from the perinuclear sarcoplasm to t he periphery of the myocytes was observed, and furthermore, secretion of ANP was significantly decreased. The microtubule network were not s tructurally affected by the PKC inhibitors. Down-regulation of PKC by 12-0-tetradecanoylphorbol 13-acetate (TPA) for 12 h was not followed b y any alteration of localization of specific granules, and the amount of secreted ANP was still considerable. Treating the down-regulated cu ltures with staurosporine, secretion of ANP was still significantly re duced. The present results suggest that the decreased ANP secretion an d the translocation of ANP-containing specific granules in the atrial myocytes following treatment with staurosporine or H7, is mediated thr ough mechanisms not, or only partly, requiring PKC.