Serotonin N-acetyltransferase and its regulation by pineal substances.

The regulation of activity of serotonin N-acetyltransferase (NAT) in pineal glands of various mammalian hierarchies may be species-specific, mediated by different mechanisms and brought about by interactions with dissimilar receptor sites. In addition to norepinephrine, serotonin and gamma-aminobutyric acid (GABA) seem to modulate NAT activity. Furthermore, preliminary studies provide evidence for the existence in pineal gland of a thermo-stable proteinaceous substance (NIS) which inactivates NAT but not other enzymes involved in the synthesis of melatonin. Inactivation of NAT by NIS is blocked by addition of 0.5 mM acetyl coenzyme A, but not coenzyme A, 0.1 M NaF or 4 mM beta-mercaptoethanol. In addition, protein dephosphorylation and disulfide exchange mechanisms are not involved in this NIS-mediated inactivation of NAT. In rat brain, the inactivating substance was found only in the pineal gland and was undetectable in other tissues. We postulate that the collective interaction among norepinephrine, serotonin, GABA, acetyl coenzyme A, NIS and NAT may regulate the synthesis of melatonin in the pineal gland.