PROTEIN-KINASE-C MODULATES NATRIURETIC PEPTIDE RECEPTORS IN ASTROGLIAL CULTURES FROM RAT-BRAIN

We determined previously that astroglia cultured from newborn rat brai n contain both guanylyl cyclase-coupled and atrial natriuretic peptide (ANP)-C natriuretic peptide receptors. Here, we investigated the effe cts of the protein kinase C (PKC) activator phorbol 12-myristate 13-ac etate (PMA) on these receptor subtypes in cultured astroglia to unders tand the intracellular processes involved in the modulation of natriur etic peptide receptors in these cells. PMA (10 nM to 1 mu M; 15 min to 24 h) treatment elicited a time- and concentration-dependent decrease in the numbers of I-125-labeled ANP specific binding sites, which was inhibited by the PKC antagonist staurosporine (500 nM). Furthermore, PMA. (100 nM, 2 or 24 h) treatment elicited a significant decrease in the specific binding of I-125-des-Cys-Cys-ANP, an ANP-C receptor selec tive ligand. PMA (10 nM to 1 mu M; 30 min) treatment also significantl y decreased ANP (100 nM)-stimulated guanosine 3',5'-cyclic monophospha te levels in cultured astroglia, an effect unmodified by phosphodieste rase inhibition. These data indicate that PKC modulates both guanylyl cyclase-coupled and ANP-C natriuretic peptide receptors in cultured as troglia.