ABSTRACT
Melatonin, the principal secretory product of the pineal gland, is known to in—uence a variety of biological processes including circadian rhythms, neuroendocrine, cardiovascular or immune functions [1]. It is an indoleamine discovered by Lerner et al. in 1958 in the pineal gland [2], which was initially considered to be the primary source of this circulating hormone, but more recently, this indoleamine was found to be a ubiquitous molecule generated by neuroendocrine cells in various tissues, particularly in the gastrointestinal tract (GIT) [3], where it was found in many folds in amounts larger than those synthesized in the pineal gland. Experimental studies in animals demonstrated that melatonin acts in a paracrine fashion on GIT mucosa and, in part, it is released to portal circulation to be up-taken by the liver for metabolism and excretion with the bile to small bowel and then to go to enterohepatic circulation [4]. Melatonin is a derivative of an essential amino acid, l-tryptophan (l-Try), synthesized in a four-step pathway. First, l-Try is converted to 5-hydroxytryptophan by tryptophan 5-monooxygenase. The aromatic 1-amino acid decarboxylase then catalyzes the conversion of 5-hydroxytryptophan to serotonin (5-hydroxytryptamine). Arylalkylamine-Nacetyltrasferase (AANAT) acetylates serotonin to N-acetylserotonin, the immediate precursor of melatonin. The last step in this biosynthetic pathway is catalyzed by hydroxyindol-O-methyltransferase (HIOMT), which leads to the formation of melatonin [5]. All these melatonin biosynthetic pathway steps and involved enzymes have been identi£ed in the rat gastric mucosa exposed to l-Try-rich diet, which accelerated the healing of gastric ulcerations [4].
