Hormone sensitivity of particulate pineal guanylate cyclase

Guanylate cyclase was studied in vitro using crude plasma membrane fractions of bovine and rabbit pineals. The particulate quanylate cyclase was stimulated 1.5-to 6-fold by the non-ionic detergent triton X-100. The effects of various adrenergic agents and pineal indoles were also tested. Serotonin, the endogenous precursor to the pineal hormone melatonin, stimulated particulate guanylate cyclase with optimal stimulation at 10-5 M. Melatonin inhibited particulate guanylate cyclase, with a maximal inhibition of 85% at 10-3 M. The adrenergic agents isoproterenol ( a ?-agonist) and phenylephrine (an ?-agonist) inhibited the particulate guanylate cyclase 95% and 75%, respectively. The endogenous adrenergic neurotransmitter, norepinephrine, had no effect on pineal particulate guanylate cyclase. Combinations of ?- and ?-agonists were effective inhibitors at concentrations that had no effect if either agent was added alone. Stimulation of guanylate cyclase by serotonin and inhibition by melatonin imply the possibility that these two endogenous pineal indoles may play a role in feedback control of pineal cGMP metabolism, and possible other pineal functions.