STIMULATORY EFFECTS OF BRAIN NATRIURETIC PEPTIDE ON CYCLIC-GMP ACCUMULATION AND TYROSINE-HYDROXYLASE ACTIVITY IN CULTURED BOVINE ADRENAL-MEDULLARY CELLS

We studied the effect of brain natriuretic peptide (BNP) on the accumulation of cyclic GMP and the phosphorylation and activity of tyrosine hydroxylase, compared with that of atrial natriuretic peptide (ANP), in cultured bovine adrenal medullary cells. 1. BNP as well as ANP increased cellular cyclic GMP accumulation in a concentration-dependent manner (10-1000 nmol/l). BNP (1-mu-mol/l) and ANP (1-mu-mol/l) produced a 60-fold and 30-fold increase in cyclic GMP accumulation, respectively. 2. The stimulatory effects of BNP and ANP on cyclic GMP accumulation were observed even when Ca2+ or Na+ was removed from the incubation medium. 3. 12-O-Tetradecanoylphorbol 13-acetate (TPA), an activator of protein kinase C, inhibited the stimulatory effect of BNP on cyclic GMP accumulation in a concentration-dependent manner (1 - 100 nmol/l). Furthermore, the BNP-induced accumulation of cyclic GMP was attenuated by forskolin (1-mu-mol/l), an activator of adenylate cyclase. 4. BNP (1-mu-mol/l) and ANP (1-mu-mol/l) caused a significant increase in phosphorylation and activity of tyrosine hydroxylase in the cells. 5. In digitonin-permeabilized cells, cyclic GMP (1 - 100-mu-mol/l) activated tyrosine hydroxylase in the presence of ATP and Mg2+. These results suggest that BNP stimulates the accumulation of cyclic GMP in a manner similar to that of ANP. The increased accumulation of cyclic GMP by these peptides may be negatively modulated by protein kinase C and cyclic AMP and may cause the phosphorylation and activation of tyrosine hydroxylase in cultured bovine adrenal medullary cells.