NYCTOHEMERAL RHYTHM IN THE LEVELS OF S-ADENOSYLMETHIONINE IN THE RAT PINEAL-GLAND AND ITS RELATIONSHIP TO MELATONIN BIOSYNTHESIS

Liquid chromatographic techniques that permit the simultaneous analysi s of S-adenosylmethionine, melatonin, and its intermediary metabolites N-acetyl-5-hydroxytryptamine and 5-hydroxytryptamine within individua l pineal glands have been developed. S-Adenosylmethionine has been sho wn to undergo a marked nyctohemeral rhythm in the pineal gland of the rat, with maximal levels occurring during the light period and minimal levels during the dark period. Detailed studies of the temporal relat ionships between the levels of S-adenosylmethionine and those of melat onin and its intermediary metabolites suggest that an association exis ts between the levels of S-adenosylmethionine and the status of the bi osynthesis of melatonin. Exposure of animals to continuous light and t he administration of the beta-adrenoreceptor antagonist propranolol we re both found to inhibit the induction of melatonin synthesis and prev ent the reduction in the levels of S-adenosylmethionine during the dar k period, As a corollary the induction of melatonin biosynthesis follo wing the administration of the beta-adrenoreceptor agonist isoproteren ol during the light period was accompanied by a marked decrease in the levels of S-adenosylmethionine in the pineal gland. The significance of the link between the nyctohemeral rhythms in the levels of S-adenos ylmethionine and the biosynthesis of melatonin in the pineal gland is discussed in the context of the therapeutic efficacy of S-adenosylmeth ionine as an antidepressant.