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-adrene rgic receptors. The effects of N(G)-monomethyl-L-arginine (NMMA), whic h inhibits nitric oxide (NO) synthase and NO-mediated activation of cy tosolic guanylate cyclase, and methylene blue (MB), which inhibits cyt osolic guanylate cyclase, were investigated in an attempt to understan d the role of NO in adrenergic cGMP formation. Both NMMA and MB inhibi ted beta-adrenergic stimulation of cGMP formation as well as alpha1-ad renergic potentiation of beta-adrenergic stimulation of cGMP formation , whereas they had no effect in unstimulated pinealocytes. The inhibit ory action of NMMA was antagonized by addition of L-arginine. On the b asis of these findings it can be concluded that the adrenergic stimula tion of cGMP formation involves NO synthesis followed by activation of cytosolic guanylate cyclase.