Complex Control of the Circadian Rhythm in N-Acetyltransferase Activity in the Rat Pineal Gland

Abstract

The enzyme N-acetyltransferase (acetyl CoA: arylamine N-acetyltransferase, EC 2.3.1.5) (NAT) acetylates serotonin to N-acetylserotonin, precursor of melatonin (Weissbach et al. 1960). In the rat pineal gland, NAT activity exhibits a circadian rhythm, persisting in constant darkness, with night values 30–100 times higher than daytime values (Klein and Weiler 1970). The rhythm is generated by daily changes in the turnover and presumably in the release of noradrenaline from sympathetic fibres innervating the pineal gland (Brownstein and Axelrod 1974). Noradrenaline released at night in darkness interacts with the beta-adrenergic receptors on the pineal cell membrane, enhancing the production of cAMP which mediates the induction of NAT (Klein and Berg 1970). Activated beta-adrenergic receptors are necessary not only for the evening NAT induction but also for the maintenance of the high night NAT activity (Deguchi and Axelrod 1972a). The NAT rhythm is abolished by denervation of the pineal gland through bilateral cervical ganglionectomy or decentralization of the ganglia (Klein et al. 1971), by destruction of the suprachiasmatic nuclei in the hypothalamus (Moore and Klein 1974) or by constant light (Klein and Weiler 1970).