Histamine H(3) 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 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.
Department of Human Anatomy, Pharmacology and Forensic Medicine, Section of Pharmacology, University of Parma, Parma, Italy.
Maristella
M
Adami
Cristina
C
Pozzoli
Rob
R
Leurs
Holger
H
Stark
Gabriella
G
Coruzzi
D000818:Animals; D005753:Gastric Mucosa / Q000473:pathology / Q000502:physiology*; D054439:Ghrelin / Q000502:physiology*; D006632:Histamine / Q000378:metabolism; D006851:Hydrochloric Acid / Q000633:toxicity; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018100:Receptors, Histamine H3 / Q000378:metabolism*
D054439:Ghrelin; D018100:Receptors, Histamine H3; D006632:Histamine; D006851:Hydrochloric Acid