Localization and biological activities of melatonin in intact and diseased gastrointestinal tract

Konturek, S.J., Konturek, P.C., Brzozowska, I., Pawlik, M., Sliwowski, Z., Czesnikiewicz-Guzik, M. , Kwiecien, S., Brzozowski, T., Bubenik, G.A. and Pawlik, W.W. (2007) Localization and biological activities of melatonin in intact and diseased gastrointestinal tract. Journal of Physiology and Pharmacology, 58(3), pp. 381-405.

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Abstract

Melatonin (MT), an indole formed enzymatically from L-trytophan (Trp), was first discovered in the bovine pineal gland in 1958 by Lerner et al. Melatonin is the most versatile and ubiquitous hormonal molecule produced not only in the pineal gland but also in various other tissues of invertebrates and vertebrates, particularly in the gastrointestinal tract (GIT). This review focuses on the localization, production, metabolism and the functions of MT in GIT and the duodenal unit (liver, biliary routes and pancreas), where multi-step biosynthetic pathways of this indole, similar to those in pinealocytes, have been identified. These biosynthetic steps of MT, including two major rate limiting enzymes; arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT), transforming L-tryptophan (Trp), originally identified in pinealocytes, have been also detected in entero-endocrine (EE) cells of GIT, where this indole appears to act in endocrine, paracrine and/or luminal pathway directly or through G-protein coupled MT receptors. Studies of the distribution of MT in GIT mucosa showed that this indole is generated in GIT in much larger amounts than it is produced in the pineal gland. Melatonin acts in GIT, partly locally in paracrine fashion and is partly released into portal circulation, to be taken up by the liver. It is then metabolized and excreted with the bile to small bowel and finally returns to liver through entero-hepatic circulation. The production of MT by the pineal gland shows circadian rhythm with high night-time surge, especially at younger age, followed by the fall during the day-light time. As a highly lipophylic substance, MT reaches all body cells within minutes, thus, serving as a convenient circadian timing signal. Following pinealectomy, the light/dark cycle of plasma MT levels disappears, while its day-time blood concentration is maintained mainly due to its release from the GIT. According to our experience, after oral application of Trp, the plasma MT increases in dose-dependent manner both in intact and pinealectomized animals and humans, indicating that GIT but not the pineal gland is a source of this indole. In GIT MT exhibits a wide spectrum of activities such as circadian entrainment, antioxidant and free radicals scavenging activity, cytoprotective, anti-inflammatory and healing efficacy of various GIT lesions such as esophagitis, gastritis, peptic ulcer, pancreatitis and colitis. This review concentrates on the generation and pathophysiological implication of MT in GIT and related organs.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Czesnikiewicz-Guzik, Dr Marta
Authors: Konturek, S.J., Konturek, P.C., Brzozowska, I., Pawlik, M., Sliwowski, Z., Czesnikiewicz-Guzik, M., Kwiecien, S., Brzozowski, T., Bubenik, G.A., and Pawlik, W.W.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
Journal Name:Journal of Physiology and Pharmacology
ISSN:0867-5910
ISSN (Online):1899-1505

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