ADRENERGIC-STIMULATION OF CYCLIC-GMP FORMATION REQUIRES NO-DEPENDENT ACTIVATION OF CYTOSOLIC GUANYLATE-CYCLASE IN RAT PINEALOCYTES

Cyclic GMP (cGMP) formation in rat pinealocytes is regulated through a synergistic dual receptor mechanism involving beta- and alpha1-adrenergic receptors. The effects of N(G)-monomethyl-L-arginine (NMMA), which inhibits nitric oxide (NO) synthase and NO-mediated activation of cytosolic guanylate cyclase, and methylene blue (MB), which inhibits cytosolic guanylate cyclase, were investigated in an attempt to understand the role of NO in adrenergic cGMP formation. Both NMMA and MB inhibited beta-adrenergic stimulation of cGMP formation as well as alpha1-adrenergic potentiation of beta-adrenergic stimulation of cGMP formation, whereas they had no effect in unstimulated pinealocytes. The inhibitory action of NMMA was antagonized by addition of L-arginine. On the basis of these findings it can be concluded that the adrenergic stimulation of cGMP formation involves NO synthesis followed by activation of cytosolic guanylate cyclase.