title: Both α2B- and α2C-adrenoceptor subtypes are involved in the mediation of centrally induced gastroprotection in mice.
abstract: α(2)-adrenoceptors are known to mediate gastroprotective effect in both acid-dependent and acid-independent ulcer models. The aim of the present study was to determine, which of the three α(2)-adrenoceptor subtypes (α(2A), α(2B) or α(2C)) is responsible for this protection. Various α(2)-adrenoceptor agonists and antagonists were administered intracerebroventricularly (i.c.v.) to C57BL/6 mice with deletion of genes encoding the different subtypes. The gastric mucosal damage was induced by orally injected acidified ethanol. Both the non-selective α(2)-adrenoceptor agonist clonidine (0.3-2.8 nmol) and the α(2B/C)-adrenoceptor subtype preferring agonist ST-91 (0.5-11.5 nmol) induced dose-dependent gastroprotective effect in wild type, α(2A)-, α(2B)- and α(2C)-KO mice. In contrast, the α(2A)-adrenoceptor subtype agonist oxymetazoline (0.07-84 nmol i.c.v.) reduced only slightly the development of ethanol-induced ulcers. The effect of clonidine was antagonized by the non-selective antagonist yohimbine (25 nmol) and the α(2B/C)-adrenoceptor antagonist ARC 239 (10.4 nmol), but not by the α(2A)-adrenoceptor antagonist BRL 44408 (7.5 nmol). ARC 239 also reversed the effect of clonidine in α(2A)-, α(2B)- and α(2C)-KO mice, while the selective α(2C)-adrenoceptor antagonist JP 1302 (52 nmol) antagonized that only in α(2B)-KO, but not in α(2A)- and α(2C)-KO mice. These results suggest that α(2B)- and α(2C)-adrenoceptor subtypes can equally contribute to the mediation of gastroprotective effect induced by α(2)-adrenoceptor agonists in mice.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4., 1089, Budapest, Hungary.
authors.forename: Zoltán S
authors.initials: ZS
authors.lastname: Zádori
authors.forename: Nashwan
authors.initials: N
authors.lastname: Shujaa
authors.forename: Serena B
authors.initials: SB
authors.lastname: Brancati
authors.forename: Lutz
authors.initials: L
authors.lastname: Hein
authors.forename: Klára
authors.initials: K
authors.lastname: Gyires
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000431:Ethanol; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020011:Protective Agents / Q000494:pharmacology*; D018341:Receptors, Adrenergic, alpha-2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D020011:Protective Agents; D018341:Receptors, Adrenergic, alpha-2; D000431:Ethanol; C011266:ST 91; D003000:Clonidine