Role of nitric oxide in pathogenesis of serotonine-induced gastric lesions in rats

Pharmacol Res. 1997 Oct;36(4):333-8. doi: 10.1006/phrs.1997.0238.


We investigated the role of nitric oxide (NO) in the development of gastric mucosal lesions induced by serotonine (5-HT) in rats. Repeated subcutaneous administration of 5-HT (20 mg kg-1) produced damage in the stomach with severe edema in the submucosa. Gastric lesions induced by 5-HT were prevented by simultaneous administration of aminoguanidine, a selective inducible NO synthase (iNOS) inhibitor, as well as by methysergide, a 5-HT antagonist. In addition, the lesions were inhibited by pretreatment with the antioxidative drugs, such as allopurinol (a xanthine oxidase inhibitor) and hydroxyurea (a neutrophil reducing agent). Following 5-HT treatment, the Ca(2+)-independent NOS activity in the gastric mucosa was significantly increased within 6 h and remained elevated for 2 days thereafter. The serum NOx levels increased 12 h after the administration of 5-HT, reaching a peak 24 h later. Gastric mucosal thiobarbituric acid (TBA) reactants and myeloperoxidase (MPO) activity were also significantly increased after 2 days treatment with 5-HT. Our results suggest that: (1) the repeated administration of 5-HT induced inflammatory gastric lesions in the rat stomach; (2) iNOS is upreguated during 5-HT treatment, and NO produced by iNOS contributes to development of gastric lesions in response to 5-HT, in addition to the oxyradical formation, and (3) the deleterious role of NO in this model may be accounted for by a cytotoxic action of peroxynitrite that is formed in the presence of NO and superoxide radicals.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Enzyme Inhibitors / pharmacology
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / metabolism
  • Gastritis / chemically induced*
  • Gastritis / etiology*
  • Gastritis / metabolism
  • Guanidines / pharmacology
  • Lipid Peroxidation
  • Male
  • Nitric Oxide / physiology*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / toxicity*


  • Enzyme Inhibitors
  • Guanidines
  • Nitric Oxide
  • Serotonin
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • pimagedine