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

被引:15
|
作者
Sibilia, V
Torsello, A
Pagani, F
Rapetti, D
Lattuada, N
Locatelli, V
Bulgarelli, I
Guidobono, F
Netti, C
机构
[1] Univ Milan, Dept Pharmacol Chemotherapy & Med Toxicol, I-20129 Milan, Italy
[2] Univ Milan, Dept Expt & Environm Med & Biotechnol, Bicocca, Italy
关键词
gastric ulcer; hexarelin; ghrelin; GHS-R antagonist; nitric oxide synthase;
D O I
10.1016/j.peptides.2004.08.001
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-Lys(3))-GRPR-6 and by the inhibitor of NO-synthase (NOS) N-omega-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. (C) 2004 Elsevier Inc. All rights reserved.
引用
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页码:2163 / 2170
页数:8
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