Effects of hexarelin against acid-independent and acid-dependent ulcerogens in the rat

Peptides. 2004 Dec;25(12):2163-70. doi: 10.1016/j.peptides.2004.08.001.

Abstract

The effects of intracerebroventricular (icv) or subcutaneous (sc) hexarelin (Hexa) administration, against gastric ulcers induced by ethanol (50%, 1 ml/rat/os) or Indomethacin (20 mg/kg/os) were examined in conscious rats. Hexa at 1 nmol/rat, icv or 10 nmol/kg, sc reduced ethanol-induced ulcers by 47% and 32% respectively. Hexa, but not ghrelin significantly worsened (+40%) Indomethacin-induced ulcers when injected sc. Hexa-gastroprotection against ethanol-induced ulcers was removed by the GHS-R antagonist (D-Lys3)-GRPR-6 and by the inhibitor of NO-synthase (NOS) Nomega-nitro-L-arginine methyl ester. Semiquantitative RT-PCR assay of gastric NOS mRNA isoforms revealed that the reduction in iNOS-derived NO and the increase of constitutive-derived NO are relevant for the gastroprotection of Hexa against ethanol-induced gastric damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ethanol
  • Gastric Mucosa / enzymology
  • Ghrelin
  • Indomethacin
  • Injections, Intraventricular
  • Injections, Subcutaneous
  • Male
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nerve Tissue Proteins / analysis
  • Nitric Oxide Synthase / analysis
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase Type I
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Oligopeptides / administration & dosage
  • Oligopeptides / pharmacology*
  • Peptide Hormones
  • Rats
  • Rats, Sprague-Dawley
  • Stomach Ulcer / chemically induced*
  • Stomach Ulcer / drug therapy*

Substances

  • Ghrelin
  • Nerve Tissue Proteins
  • Oligopeptides
  • Peptide Hormones
  • hexarelin
  • Ethanol
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Nos1 protein, rat
  • Nos2 protein, rat
  • Nos3 protein, rat
  • NG-Nitroarginine Methyl Ester
  • Indomethacin