κ阿片激动剂的致心律失常作用涉及百日咳毒素敏感的G蛋白机制

Pertussis toxinsensitive G proteins involved in the arrhythmogenic effect of κ opioid agonist

目的：探讨百日咳毒素（ＰＴＸ）敏感的Ｇ蛋白是否介导κ阿片激动剂的心脏效应。方法：应用离体大鼠心脏Ｌａｎｇｅｎｄｏｒｆ灌流模型观察κ阿片激动剂Ｕ５０４８８Ｈ的心脏作用并探讨其可能机制。结果：研究结果表明，Ｕ５０４８８Ｈ可导致心律失常、降低心率、心肌收缩力量和冠脉流量；ＭＲ２２６６和百日咳毒素（ＰＴＸ）预处理后，可取消Ｕ５０４８８Ｈ的致心律失常作用，但不能取消其降低心肌收缩力量和冠脉流量的作用。结论：结果提示κ阿片激动剂的致心律失常作用涉及ＰＴＸ敏感的Ｇ蛋白机制。

AIM: To explore whether pertussis toxinsensitive G protein is involved in the cardiac effect of κ opioid agonist. METHODS: In the present study, the Langendorff isolated perfused rat heart was used as a model for study of cardiac effect of κ agonist and its possible mechanisms. RESULTS: It was shown that U50488 H induced arrhythmias, reduced heart rate, myocardial contractile force and coronary flow. Pretreatment with MR2266, a specific κ antagonist, and pertussis toxin, which ribosylates and inactivates the Gilike proteins, abolished the arrhythmogenic effect of U50488 H, but failed to cancel the reduction of contractile force and coronary flow induced by U50488 H. CONCLUSION: The results suggested that the arrhythmogenic effect of κ opioid agonist U50488 H on the isolated rat heart involved pertussis toxinsensitive G proteins.