Dynamic physiological and molecular changes in gastric ulcer healing achieved by melatonin and its precursor L-tryptophan in rats

Peter C. Konturek, Stanislaw J. Konturek, Grzegorz Burnat, Tomasz Brzozowski, Iwona Brzozowska, Russel J. Reiter

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Following induction of gastric ulcer in rats by serosal application of acetic acid, local mucosal necrosis ensues accompanied by a reduction in mucosal microcirculation and by almost immediate expression of inducible nitric oxide (NO) synthase (iNOS) and proinflammatory cytokines. Daily application of melatonin (20 mg/kg) or l-tryptophan (100 mg/kg) accelerates ulcer healing by affecting the cyclooxygenase-2 (COX-2)-prostaglandin (PG) system with excessive production of protective PG, especially in later period of ulcer healing. Furthermore, expression of hypoxia inducible factor, vascular-endothelial growth factor, an activation of cNOS-NO system and the stimulation of sensory nerves with the expression and release of calcitonin gene related peptide (CGRP) appear to aid the restoration of mucosal repair and microcirculation in the ulcer bed. The enhanced expression of the melatonin MT2 receptors (MT 2-R) combined with overexpression of key enzymes involved in biosynthesis of melatonin such as N-acetyltransferase and hydroxyindole-O- methyltransferase contribute to the acceleration of ulcer healing by this indole. Melatonin-induced acceleration of ulcer healing is also mediated by release of gastrin and ghrelin, the most potent stimulants of gastric mucosal cell proliferation and mucosal repair. These sequential steps in ulcer healing accelerated by melatonin can be interfered with by the blockade of MT 2R, COX-2/PG and cNOS/NO systems, and by reduction in the inflammatory iNOS/NO system. Thus, melatonin and its precursor l-tryptophan, trigger the cascade of molecular events leading to the functional improvement in ulcer healing.

Original languageEnglish (US)
Pages (from-to)180-190
Number of pages11
JournalJournal of pineal research
Volume45
Issue number2
DOIs
StatePublished - Sep 1 2008

Keywords

  • Cyclooxygenase-1
  • Cyclooxygenase-2
  • Gastric ulcer
  • Inducible nitric oxide synthase
  • Melatonin
  • Nitric oxide
  • Prostaglandins
  • Sensory nerves
  • cNOS

ASJC Scopus subject areas

  • Endocrinology

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