Histamine H3 Receptors Are Involved in the Protective Effect of Ghrelin against HCl-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 HCl and the involvement of histamine H 3 receptors (H 3 Rs) were investigated in conscious rats with selective H 3 R ligands. Intraperitoneal (i.p.) injection of ghrelin (40 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 g/kg i.p.) and by subcutaneous (s.c.) injection of the nonimidazole H 3 R antagonist UCL2138 (30 mg/kg). The selective H 3 R 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 -Lys 3 ]-GHRP-6 (100  g/kg i.p.). Neither [ D -Lys 3 ]-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 Received: July 14, 2010 Accepted: July 31, 2010 Published online: October 22, 2010 Prof. Gabriella Coruzzi Department of Human Anatomy, Pharmacology and Forensic Medicine Section of Pharmacology, Via Volturno 39 IT–43100 Parma (Italy) Tel. +39 0521 903 851, Fax +39 0521 903 852, E-Mail gabriella.coruzzi @ unipr.it © 2010 S. Karger AG, Basel 0031–7012/10/0866–0259$26.00/0 Accessible online at: www.karger.com/pha D ow nl oa de d by : 54 .7 0. 40 .1 1 11 /1 9/ 20 17 1 2: 28 :1 8 P M