Alpha-2-adrenoceptor hyporesponsiveness in isolated tissues of cholestatic animals: Involvement of opioid and nitric oxide systems

Shadpour Demehri, Khodadad Namiranian, Shahram Ejtemaei Mehr, Hossein Rastegar, Ahamd Shariftabrizi, Seyed Ali Gaskari, Farshad Roushanzamir, Ahmad Reza Dehpour

Research output: Contribution to journalArticle

Abstract

In the present study, the status of α2-adrenoceptors during cholestasis was investigated by the inhibitory effect of clonidine on the electrically stimulated contractions of mice vas deferens (MVD) and guinea pig ileum (GPI). Clonidine inhibited the contractions in both tissues in a dose-dependent manner. Compared to unoperated animals, there was a significant right-shift in the clonidine concentration-curves of both tissues obtained from 5-day bile-duct ligated (BDL) animals (p < 0.01), implying the hyporesponsiveness of α2-adrenoceptors during cholestasis. Chronic treatment with naltrexone (3 mg/kg/day) reversed the right-shift induced by cholestasis in both tissues. Administration of N(ω)-nitro-L-arginine methyl ester (20 mg/kg/day) also partially reversed cholestasis-induced effect on IC50 of clonidine. These two treatments had no effect on IC50 of tissues from controls. Chronic yohimbine treatment (5 mg/kg/day) recovered the effect of cholestasis on MVD, but sensitized the ileum of unoperated and BDL guinea pigs to clonidine to a similar extent, providing evidence for the role of the augmented adrenergic state of cholestasis in the hyporesponsiveness of norepinephrine-releasing neurons of MVD. We concluded that cholestasis is associated with the decreased responsiveness of α2-adrenoceptors and the cholestasis-associated augmented opioidergic tone and increased NO production contribute to this process.

Original languageEnglish (US)
Pages (from-to)209-220
Number of pages12
JournalLife Sciences
Volume73
Issue number2
DOIs
StatePublished - May 30 2003
Externally publishedYes

Keywords

  • Alpha-2-adrenoceptors
  • Cholestasis
  • Guinea pig ileum
  • Mice vas deferens
  • Nitric oxide
  • Opioid

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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