TY - JOUR
T1 - Alpha-2-adrenoceptor hyporesponsiveness in isolated tissues of cholestatic animals
T2 - Involvement of opioid and nitric oxide systems
AU - Demehri, Shadpour
AU - Namiranian, Khodadad
AU - Mehr, Shahram Ejtemaei
AU - Rastegar, Hossein
AU - Shariftabrizi, Ahamd
AU - Gaskari, Seyed Ali
AU - Roushanzamir, Farshad
AU - Dehpour, Ahmad Reza
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2003/5/30
Y1 - 2003/5/30
N2 - 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.
AB - 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.
KW - Alpha-2-adrenoceptors
KW - Cholestasis
KW - Guinea pig ileum
KW - Mice vas deferens
KW - Nitric oxide
KW - Opioid
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U2 - 10.1016/S0024-3205(03)00258-3
DO - 10.1016/S0024-3205(03)00258-3
M3 - Article
C2 - 12738035
AN - SCOPUS:0038063032
SN - 0024-3205
VL - 73
SP - 209
EP - 220
JO - Life Sciences
JF - Life Sciences
IS - 2
ER -