Effects of hexarelin against acid-independent and acid-dependent ulcerogens in the rat.
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.
Sibilia
V
V
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milano, Via Vanvitelli 32, 20129 Milano, Italy. Valeria.Sibilia@unimi.it
Torsello
A
A
Pagani
F
F
Rapetti
D
D
Lattuada
N
N
Locatelli
V
V
Bulgarelli
I
I
Guidobono
F
F
Netti
C
C
D000818:Animals; D000431:Ethanol; D005753:Gastric Mucosa / Q000201:enzymology; D054439:Ghrelin; D007213:Indomethacin; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D036361:Peptide Hormones; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000188:drug therapy*
D054439:Ghrelin; D009419:Nerve Tissue Proteins; D009842:Oligopeptides; D036361:Peptide Hormones; C086184:hexarelin; D000431:Ethanol; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin