论文部分内容阅读
AIM:To investigate the role of opioid μ-receptor subtype in opiate-induced constipation (OIC).METHODS:The effect of loperamide on intestinal transit was investigated in mice.Ileum strips were isolated from 12-wk-old male BALB/c mice for identification of isometric tension.The ileum strips were precontracted with 1 μmol/L acetylcholine (ACh).Then,decrease in muscle tone (relaxation) was characterized after cumulative administration of 0.1-10 μmol/L loperamide into the organ bath,for a concentration-dependent study.Specific blockers or antagonists were used for pretreatment to compare the changes in loperamide-induced relaxation.RESULTS:In addition to the delay in intestinal transit,loperamide produced a marked relaxation in isolated ileum precontracted with ACh,in a dose-dependent manner.This relaxation was abolished by cyprodime,a selective opioid μ-receptor antagonist,but not modified by naloxonazine at a dose sufficient to block opioid μ-1 receptors.Also,treatment with opioid μ-1 receptor agonist failed to modify the muscle tone.Moreover,the relaxation by loperamide was attenuated by glibenclamide at a dose sufficient to block ATP-sensitive K + (K ATP) channels,and by protein kinase A (PKA) inhibitor,but was enhanced by an inhibitor of phosphodiesterase for cyclic adenosine monophosphate (cAMP).CONCLUSION:Loperamide induces intestinal relaxation by activation of opioid μ-2 receptors via the cAMPPKA pathway to open K ATP channels,relates to OIC.
AIM: To investigate the role of opioid μ-receptor subtype in opiate-induced constipation (OIC). METHODS: The effect of loperamide on intestinal transit was investigated in mice. Ileum strips were isolated from 12-wk-old male BALB / c mice for identification of isometric tension. The ileum strips were precontracted with 1 μmol / L acetylcholine (ACh). Try, decrease in muscle tone (relaxation) was characterized after cumulative administration of 0.1-10 μmol / L loperamide into the organ bath, for a concentration-dependent study. Specific blockers or antagonists were used for pretreatment to compare the changes in loperamide-induced relaxation. RESULTS: In addition to the delay in intestinal transit, loperamide produced a marked relaxation in isolated ileum precontracted with ACh, in a dose- dependent manner. This relaxation was abolished by cyprodime, a selective opioid μ-receptor antagonist, but not modified by naloxonazine at a dose sufficient to block opioid μ-1 receptors. Als, treatment with opioid μ -1 receptor agonist failed to modify the muscle tone. More of the relaxation by loperamide was attenuated by glibenclamide at a dose sufficient to block ATP-sensitive K + (K ATP) channels, and by protein kinase A (PKA) inhibitor, but was enhanced by an inhibitor of phosphodiesterase for cyclic adenosine monophosphate (cAMP). CONCLUSION: Loperamide induces intestinal relaxation by activation of opioid μ-2 receptors via the cAMPPKA pathway to open K ATP channels, to OIC.