PINEAL NITRIC-OXIDE SYNTHASE - CHARACTERISTICS, ADRENERGIC REGULATIONAND FUNCTION

Available studies indicate that the adrenergic stimulation of pineal c yclic GMP production involves stimulation of guanylyl cyclase activity by nitric oxide (NO) derived from arginine. This line of investigatio n was extended in the present study. Using a highly sensitive microass ay, it was found that pineal NO synthase activity is present at levels similar to 30% of those in the cerebellum, that approximately 95% of enzyme activity is cytoplasmic, that the enzyme is Ca2+/calmodulin-dep endent and that enzyme activity is inhibited by the arginine analog N- G-nitro-L-arginine methyl ester (L-NAME). Norepinephrine treatment of intact glands in culture increased [H-3]citrulline formation from [H-3 ]arginine. This treatment also increased the formation of an NO-like c ompound, indicating that NO synthase activity in the intact gland is e levated by adrenergic stimulation. Studies on the effects of inhibitio n of NO synthase activity indicated that treatments known to inhibit N O synthase activity and the adrenergic stimulation of cyclic GMP accum ulation did not inhibit adrenergic stimulation of pineal cyclic AMP, N -acetyltransferase activity or melatonin production. These observation s support the hypothesis that NE stimulation of pineal cyclic GMP accu mulation involves stimulation of a Ca2+/calmodulin-sensitive form of N O synthase, resulting in enhanced accumulation of NO; and, that althou gh NO appears to play a role in the adrenergic stimulation of pineal c yclic GMP accumulation, it does not appear to play a critical role in the adrenergic stimulation of cyclic AMP, N-acetyltransferase activity or melatonin production.