Histamine H3 Receptors Are Involved in the Protective Effect of Ghrelin against HCI-Induced Gastric Damage in Rats

In the present study, the effects of ghrelin against the gastric damage induced by intragastric administration of 0.6 N HCI and the involvement of histamine H-3 receptors (H(3)Rs) were investigated in conscious rats with selective H3R ligands. Intraperitoneal (i.p.) injection of ghrelin (40 mu g/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-Lys(3)]-GHRP-6 (100 mu g/kg i.p.) and by subcutaneous (s.c.) injection of the nonimidazole H3R agonist 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 HCI. The effect of immethridine was prevented by prior administration of UCL2138 (30 mg/kg s.c.), but not by [D-Lys3]-GHRP-6 (100 mu g/kg i.p.). Neither [D-Lys(3)]-GHRP-6 nor UCL2138 modified NCI-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 H(3)Rs. Copyright (C) 2010 S. Karger AG, Basel