Cholinesterases in cardiac ganglia and modulation of canine intrinsic cardiac neuronal activity
Cholinesterases in cardiac ganglia and modulation of canine intrinsic cardiac neuronal activity
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DOI：
10.1016/s0165-1838(98)00064-2
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发表时间：
1998-07-15
期刊：
影响因子：
--
通讯作者：
Armour, JA
中科院分区：
文献类型：
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作者：
Darvesh, S;MacDonald, SE;Armour, JA
胆碱能神经传递在心内神经节中起重要作用，其中乙酰胆碱的作用被乙酰胆碱酯酶（AChE，EC 3.1.1.7）终止。进行解剖学研究以表征犬心内神经节中与AChE和密切相关的酶丁酰胆碱酯酶（BuChE，EC 3.1.1.8）相关的神经元。犬右心房神经元中AChE和BuChE的组织化学染色表明，有四个神经元群体，即，仅含有AChE，仅BuChE，AChE和BuChE，和那些不含任何酶。在麻醉狗上研究了心脏内神经元对胆碱酯酶底物和抑制剂的反应。通过动作电位数量的变化来测量的内在心脏神经元的活性通过局部应用乙酰胆碱而增加。然而，局部应用丁酰胆碱导致了一个相当大的增加内在的心脏神经元的活动。在保持与胆碱酯酶在心脏内神经节的神经化学异质性，最丁酰胆碱敏感的神经元产生的活动不受乙酰胆碱和产生的活动，最乙酰胆碱敏感的神经元不受丁酰胆碱的影响。这表明，这两种药物优先影响不同群体的内在心脏神经元。酶动力学研究表明，犬AChE优先催化水解乙酰胆碱，而犬BuChE优先催化水解丁酰胆碱。胆碱酯酶抑制剂Ro 2-1250和Ro 2-0638抑制犬的两种胆碱酯酶，石杉碱甲优先抑制犬的AChE和乙氧丙嗪抑制犬的BuChE。当局部给予Ro 2-1250或Ro 2-0638时，心内神经节中神经元的活性显著增加。当石杉碱甲或乙索丙嗪给药时，神经元的活性不受影响，这表明必须抑制这两种胆碱酯酶才能增加神经元的活性。总之，这些数据表明，除了乙酰胆碱酯酶，心内神经节还含有不同的群体的神经元与BuChE，这些神经元产生的活动是不同的影响，其基板。由于同时抑制乙酰胆碱酯酶和丁胆碱酯酶导致神经元活动增加，它的结论是，乙酰胆碱酯酶和丁胆碱酯酶阳性的内在心脏神经元可能会协同作用，影响整体紧张性活动的内在心脏神经节。(C)1998 Elsevier Science B. V.保留所有权利。
Cholinergic neurotransmission plays a significant role in intrinsic cardiac ganglia with the action of acetylcholine being terminated by acetylcholinesterase (AChE, EC 3.1.1.7). Anatomical studies were performed to characterize neurons associated with AChE and a closely related enzyme, butyrylcholinesterase (BuChE, EC 3.1.1.8), in canine intrinsic cardiac ganglia. Histochemical staining for AChE and BuChE in canine right atrial neurons showed that there were four neuronal populations, namely, those that contained AChE only, BuChE only, both AChE and BuChE, and those that did not contain either enzymes. The neuronal activity of intrinsic cardiac neurons in response to substrates and inhibitors of cholinesterases were studied in anesthetized dogs. The activity of intrinsic cardiac neurons, as measured by changes in the number of action potentials, increased by local application of acetylcholine. However, local application of butyrylcholine led to a considerably greater increase in the activity of intrinsic cardiac neurons. In keeping with the neurochemical heterogeneity in intrinsic cardiac ganglia with respect to cholinesterases, the activity generated by most butyrylcholine-sensitive neurons was not influenced by acetylcholine and the activity generated by, the most acetylcholine-sensitive neurons was not influenced by butyrylcholine. This suggests that these two agents preferentially influence different populations of intrinsic cardiac neurons. Enzyme kinetic studies demonstrated that canine AChE preferentially catalyzed the hydrolysis of acetylcholine while canine BuChE preferentially catalyzed the hydrolysis of butyrylcholine. Cholinesterase inhibitors Ro 2-1250 and Ro 2-0638 inhibited both canine cholinesterases, while huperzine A preferentially inhibited canine AChE and ethopropazine inhibited canine BuChE. The activity of neurons in the intrinsic cardiac ganglia significantly increased when Ro 2-1250 or Ro 2-0638 was administered locally. The activity of neurons was not affected when huperzine A or ethopropazine was administered, indicating that both cholinesterases must be inhibited to increase neuronal activity. In summary, these data show that in addition to AChE, intrinsic cardiac ganglia also contain distinct populations of neurons that are associated with BuChE, and the activity generated by these neurons is differentially influenced by their substrates. Because simultaneous inhibition of AChE and BuChE leads to increased neuronal activity, it is concluded that AChE- and BuChE-positive intrinsic cardiac neurons may act synergistically to influence the overall tonic activity of intrinsic cardiac ganglia. (C) 1998 Elsevier Science B.V. All rights reserved.