Peptidergic and cholinergic neurons and mediators in peptone-induced gastroprotection: role of cyclooxygenase-2

Am J Physiol. 1998 May;274(5):G955-64. doi: 10.1152/ajpgi.1998.274.5.G955.


This study investigates the neural pathways, mediators, and cyclooxygenase isoenzymes involved in the gastroprotection conferred by peptone in rats. Intragastric perfusion with 8% peptone protected against gross and histological damage induced by subsequent perfusion with 50% ethanol. The gastroprotective effect of peptone was near maximally inhibited by gastrin immunoneutralization, inactivation of capsaicin-sensitive afferent neurons, calcitonin gene-related peptide (CGRP) immunoneutralization, blockade of gastrin receptors, CGRP, bombesin/gastrin-releasing peptide (GRP), or somatostatin receptors, and by the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester and was partially (46%) counteracted by atropine. Indomethacin and the selective cyclooxygenase-2 inhibitors NS-398 and L-745,337 dose dependently (50% inhibitory dose, 4.2, 0.8, and 1.5 mg/kg, respectively) attenuated the peptone-induced protection. Dexamethasone was ineffective. These results indicate that protective effects of peptone involve endogenous gastrin and possibly somatostatin and are mediated by capsaicin-sensitive afferent, cholinergic, and bombesin/GRP neurons. CGRP, NO, and prostaglandins participate as essential mediators. The study provides evidence that prostaglandins derived from a constitutive cyclooxygenase-2 contribute to mucosal defense in the presence of ulcerogens and thus participate in homeostatic functions of the stomach.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Bombesin / physiology
  • Calcitonin Gene-Related Peptide / physiology
  • Cyclooxygenase 2
  • Gastric Mucosa / blood supply
  • Gastrins / physiology
  • Isoenzymes / physiology*
  • Male
  • Neurons / physiology*
  • Neurons, Afferent / physiology
  • Parasympathetic Nervous System / cytology
  • Parasympathetic Nervous System / physiology*
  • Peptides / metabolism*
  • Peptones / pharmacology*
  • Prostaglandin-Endoperoxide Synthases / physiology*
  • Rats
  • Rats, Wistar
  • Regional Blood Flow / drug effects
  • Somatostatin / physiology
  • Stomach / drug effects*


  • Gastrins
  • Isoenzymes
  • Peptides
  • Peptones
  • Somatostatin
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Calcitonin Gene-Related Peptide
  • Bombesin