Acetylcholine release in human heart atrium - Influence of muscarinic autoreceptors, diabetes, and age
Acetylcholine release in human heart atrium - Influence of muscarinic autoreceptors, diabetes, and age
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DOI：
10.1161/01.cir.103.12.1638
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发表时间：
2001-03-27
期刊：
影响因子：
37.8
通讯作者：
Rump, LC
中科院分区：
文献类型：
--
作者：
Oberhauser, V;Schwertfeger, E;Rump, LC
心脏交感神经和副交感神经驱动的失衡是冠心病、糖尿病和肾功能不全患者心源性死亡的重要危险因素。从周围自主神经释放的神经递质的量由突触前受体系统调节。在类似的铬-交感神经上的自体受体，毒蕈碱自体受体激活内源性乙酰胆碱可能存在于副交感神经在human heart.Methods和结果，我们开发了一种技术来研究乙酰胆碱释放从人心房和调查毒蕈碱自体受体功能。药理学和分子方法被用来表征亚型。在克隆的5种毒蕈碱受体亚型中，仅检测到编码M-2-和M-3-受体的mRNA。几种毒蕈碱拮抗剂对非选择性毒蕈碱激动剂卡巴胆碱在心脏自身受体的释放抑制作用的潜力与人类克隆的M-1-通过M-5-receptors.Conclusions-This分析清楚地表明，乙酰胆碱在人类心房释放的毒蕈碱M-2-受体控制的已发表的数据。阿托品阻断这些受体后，在5 Hz的刺激频率下释放的乙酰胆碱量加倍。在>70岁的患者和患有晚期糖尿病并发症的患者的心房中，乙酰胆碱释放减少。因此，局部受损的心脏乙酰胆碱释放可能代表了老年人和糖尿病患者心脏性猝死的病理生理学联系。
Background-An imbalance of sympathetic and parasympathetic drive to the heart is an important risk factor for cardiac death in patients with coronary heart disease, diabetes, and renal insufficiency. The amount of neurotransmitter released from peripheral autonomic nerves is modulated by presynaptic receptor systems. In analogy to cr-autoreceptors on sympathetic nerves, muscarinic autoreceptors activated by endogenous acetylcholine may exist on parasympathetic nerves in the human heart.Methods and Results-We developed a technique to study acetylcholine release from human atria and investigated muscarinic autoreceptor function. A pharmacological and molecular approach was used to characterize the subtype involved. Of the 5 muscarinic receptor subtypes cloned, only mRNA encoding for M-2- and M-3-receptors were detected. Potencies of several muscarinic antagonists against the release-inhibiting effect of the nonselective muscarinic agonist carbachol at the cardiac autoreceptor were correlated with published data for human cloned M-1- through M-5-receptors.Conclusions-This analysis clearly indicates that acetylcholine release in human atria is controlled by muscarinic M-2-receptors. Blockade of these receptors by atropine doubles the amount of acetylcholine released at a stimulation frequency of 5 Hz. In atria of patients >70 years of age and patients with late diabetic complications, acetylcholine release is reduced. Locally impaired cardiac acetylcholine release may therefore represent a pathophysiological link to sudden cardiac death in elderly and diabetic patients.