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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Subsensitivity to Opioids Is Receptor-Specific in Isolated Guinea Pig Ileum and Mouse Vas Deferens after Obstructive Cholestasis

Ahmad R. Dehpour, Hossein Rastegar, Masoumeh Jorjani, Farshad Roushanzamir, Khojasteh Joharchi and Abolhasan Ahmadiani
Journal of Pharmacology and Experimental Therapeutics June 2000, 293 (3) 946-951;
Ahmad R. Dehpour
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Hossein Rastegar
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Masoumeh Jorjani
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Farshad Roushanzamir
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Khojasteh Joharchi
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Abolhasan Ahmadiani
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Abstract

The rate and degree of subsensitivity development to morphine (μ-opioid receptor, preferred, but not selective agonist) and U50488H (highly selective κ-opioid receptor agonist) were assessed in vitro on guinea pig ileum (GPI) of cholestatic animals 2, 5, and 7 days after bile duct ligation. In addition to this phenomenon of morphine, the effects of U50488H and SNC 80 (highly selective δ-opioid receptor agonist) were studied in vitro on mice vas deferens (MVD) of cholestatic animals 2, 5, 7, 10, and 15 days after bile duct ligation. The IC50 for each compound was determined in these preparations. The ratio of the IC50 in bile duct-ligated animals to sham and control animals provides a quantitative index for the degree of subsensitivity development to each agonist. For any given time, the highest degree of subsensitivity to morphine was observed in GPI of cholestatic animals, whereas in MVD obtained from the cholestatic animals, the highest degree of subsensitivity developed to inhibitory effect of SNC 80. The subsensitivity development in cholestatic animals was time dependent; in GPI the maximum subsensitivity developed after 7 days of the operation, whereas the maximum subsensitivity in MVD developed 15 days after bile duct ligation. Moreover, subsensitivity to exogenous acetylcholine and norepinephrine in GPI and MVD, respectively, did not develop in the presence of subsensitivity to opioids in cholestatic animals. Significant accumulation of endogenous opioids in plasma of cholestatic animals has been shown in several studies and this may account for a significant development of subsensitivity to inhibitory effects of opioid agonists.

Footnotes

  • Send reprint requests to: Ahmad Reza Dehpour, Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran. E-mail: ardeh{at}nrcgeb.ac.ir

  • Abbreviations:
    GPI
    guinea pig ileum
    MVD
    mouse vas deferens
    β-FNA
    β-funaltrexamine
    nor-BNI
    nor-binaltorphimine
    BDL
    bile duct ligated
    • Received October 27, 1999.
    • Accepted January 13, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 293 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 293, Issue 3
1 Jun 2000
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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Subsensitivity to Opioids Is Receptor-Specific in Isolated Guinea Pig Ileum and Mouse Vas Deferens after Obstructive Cholestasis

Ahmad R. Dehpour, Hossein Rastegar, Masoumeh Jorjani, Farshad Roushanzamir, Khojasteh Joharchi and Abolhasan Ahmadiani
Journal of Pharmacology and Experimental Therapeutics June 1, 2000, 293 (3) 946-951;

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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Subsensitivity to Opioids Is Receptor-Specific in Isolated Guinea Pig Ileum and Mouse Vas Deferens after Obstructive Cholestasis

Ahmad R. Dehpour, Hossein Rastegar, Masoumeh Jorjani, Farshad Roushanzamir, Khojasteh Joharchi and Abolhasan Ahmadiani
Journal of Pharmacology and Experimental Therapeutics June 1, 2000, 293 (3) 946-951;
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