THE ROLE OF ARGININE-VASOPRESSIN FOR PINEAL MELATONIN SYNTHESIS IN THE RAT: INVOLVEMENT OF VASOPRESSINERGIC RECEPTORS

Abstract The endogenously synthesized nonapeptide arginine vasopressin (AVP) is thought to be involved in transduction of photic information to the pineal gland. The enhancement of circulating AVP leads to a suppression of the nocturnal melatonin surge the mechanisms of which are unknown so far. We therefore studied the effect of dDAVP, an AVP analog with antidiuretic but without vasopressor activity, on pineal melatonin synthesis in Sprague-Dawley and AVP-deficient Brattleboro rats. The nocturnal intra-arterial application of dDAVP mimicked the inhibitory effect of AVP on the activity of the rate-limiting enzyme for pineal melatonin synthesis, N-acetyltransferase (NAT), in both rat strains. Furthermore, since the pineal is equipped with receptors for VP 4–9 (the major proteolytic AVP fragment) only, the influence of this substance on the gland's metabolic activity was investigated in vitro. Neither this peptide nor AVP alone did affect NAT activity, but either substance potentiated the norepinephrine-induced enhancement of NAT activity. These results reveal that at least two mechanisms mediate the influence of AVP on pineal melatonin synthesis. The AVP-induced pineal inhibition in vivo is probably due to a receptor-mediated effect on pinealopetal signal transduction. This inhibition masks the potentiating effect of AVP on the pineal gland itself which is delayed by the conversion of AVP to VP 4–9 . The present results support the idea of a modulatory role of AVP and its metabolites in the generation and maintenance of the circadian melatonin rhythm in mammals.