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 ...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.展开更多
The effect of U50488, a selective K-opioid receptor agonist, on cardiac rhythm in the isolated perfused rat heart and intracellular calcium ([Ca2+] i) in the single ventricular myocyte were studied. The results showed...The effect of U50488, a selective K-opioid receptor agonist, on cardiac rhythm in the isolated perfused rat heart and intracellular calcium ([Ca2+] i) in the single ventricular myocyte were studied. The results showed that U50488 can induce arrhythmias dose-dependently in the isolated perfused rat heart and increase [ Ca2 + ] i in the single ventricular myocyte. The effect of U50488 can be blocked by a selectivek-receptor antagonist, nor-binaltorphimine. The arrhythmogenic effects and the increase of [ Ca2+]i induced by U50488 were blocked by U73122, neomycin and streptomycin, which are selective phospolipase C inhibitors, but not by U73433, the inactive structural analog of U73122. These results demonstrated that the arrhythmogenic effect of cardiac K-receptor is due to activation of phosphoinositol/Ca2+ pathway.展开更多
基金Supported by A grant from E-Da Hospital (in part)
文摘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.
文摘The effect of U50488, a selective K-opioid receptor agonist, on cardiac rhythm in the isolated perfused rat heart and intracellular calcium ([Ca2+] i) in the single ventricular myocyte were studied. The results showed that U50488 can induce arrhythmias dose-dependently in the isolated perfused rat heart and increase [ Ca2 + ] i in the single ventricular myocyte. The effect of U50488 can be blocked by a selectivek-receptor antagonist, nor-binaltorphimine. The arrhythmogenic effects and the increase of [ Ca2+]i induced by U50488 were blocked by U73122, neomycin and streptomycin, which are selective phospolipase C inhibitors, but not by U73433, the inactive structural analog of U73122. These results demonstrated that the arrhythmogenic effect of cardiac K-receptor is due to activation of phosphoinositol/Ca2+ pathway.
