INHIBITION OF CEREBELLAR NITRIC-OXIDE SYNTHASE AND CYCLIC-GMP PRODUCTION BY MELATONIN VIA COMPLEX-FORMATION WITH CALMODULIN

Constitutive rat cerebellar nitric oxide synthase (NOS) activity is sh own to be inhibited by physiological concentrations of the pineal horm one melatonin. The inhibition was dose-dependent and was coupled to an inhibition of the cyclic CMP production activated by L-arginine. Resu lts also show that calmodulin appears to be involved in this process b ecause its presence in the incubation medium was able to prevent the e ffect of melatonin on both NOS activity and cyclic GMP production. Mor eover, polyacrylamide gel electrophoresis studies suggest that melaton in can interact with calmodulin modifying the binding of the peptide t o the synthetic NOS peptide encompassing the calmodulin-binding domain of constitutive NOS from rat cerebellum, the natural mechanism by whi ch calmodulin activates cerebellar NOS. (C) 1997 Wiley-Liss, Inc.