Department of Human Anatomy, Pharmacology and Forensic Medicine, Section of Pharmacology, University of Parma, Parma, Italy.
Pharmacology. 2010;86(5-6):259-66. doi: 10.1159/000320110. Epub 2010 Oct 22.
In the present study, the effects of ghrelin against the gastric damage induced by intragastric administration of 0.6 N HCl and the involvement of histamine H₃ receptors (H₃Rs) were investigated in conscious rats with selective H₃R ligands. Intraperitoneal (i.p.) injection of ghrelin (40 μg/kg) significantly reduced (43%) the gastric lesions caused by concentrated acid. The effect of ghrelin was prevented by prior administration of the ghrelin receptor antagonist [D-Lys³]-GHRP-6 (100 μg/kg i.p.) and by subcutaneous (s.c.) injection of the nonimidazole H₃R antagonist UCL2138 (30 mg/kg). The selective H₃R agonist immethridine (30 mg/kg s.c.) significantly inhibited (64.60%) the gastric lesions induced by 0.6 N HCl. The effect of immethridine was prevented by prior administration of UCL2138 (30 mg/kg s.c.), but not by [D-Lys³]-GHRP-6 (100 μg/kg i.p.). Neither [D-Lys³]-GHRP-6 nor UCL2138 modified HCl-induced gastric damage per se. These data enlarge previous studies showing protective effects of ghrelin against ulcerogenic stimuli; in addition, they clearly indicate that ghrelin-induced gastroprotection involves the release of histamine, which enhances gastric mucosal defense through the activation of histamine H₃Rs.
在本研究中，使用选择性 H₃R 配体研究了 ghrelin 对胃内给予 0.6 N HCl 引起的胃损伤的影响及其与组胺 H₃ 受体（H₃Rs）的关系。腹腔内（i.p.）注射 ghrelin（40 μg/kg）可显著减少（43%）由浓酸引起的胃损伤。ghrelin 的作用可被 ghrelin 受体拮抗剂 [D-Lys³]-GHRP-6（100 μg/kg i.p.）预先给药和非咪唑 H₃R 拮抗剂 UCL2138（30 mg/kg s.c.）皮下注射所阻止。选择性 H₃R 激动剂 immethridine（30 mg/kg s.c.）可显著抑制（64.60%）由 0.6 N HCl 引起的胃损伤。immethridine 的作用可被 UCL2138（30 mg/kg s.c.）预先给药所阻止，但不能被 [D-Lys³]-GHRP-6（100 μg/kg i.p.）阻止。[D-Lys³]-GHRP-6 和 UCL2138 均未单独改变 HCl 引起的胃损伤。这些数据扩大了先前的研究，表明 ghrelin 对溃疡刺激具有保护作用；此外，它们清楚地表明，ghrelin 诱导的胃保护涉及组胺的释放，通过激活组胺 H₃Rs 增强胃黏膜防御。
