Both α 2B- and α 2C-adrenoceptor subtypes are involved in the mediation of centrally induced gastroprotection in mice

Zoltán S. Zádori, Nashwan Shujaa, Serena B. Brancati, Lutz Hein, Klára Gyires

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)115-120
Number of pages6
JournalEuropean Journal of Pharmacology
Volume669
Issue number1-3
DOIs
Publication statusPublished - Nov 1 2011

Keywords

  • Ethanol-induced ulcer
  • Gastroprotection
  • Knock out mouse
  • α -adrenoceptor subtype

ASJC Scopus subject areas

  • Pharmacology

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