Pre- and postsynaptic effects of muscarinic agonists in the guinea-pig ileum
Pre- and postsynaptic effects of muscarinic agonists in the guinea-pig ileum
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毒蕈碱激动剂对豚鼠回肠的突触前和突触后作用
DOI：
10.1007/bf00498547
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发表时间：
1980
期刊：
影响因子：
--
通讯作者：
I. Wessler
中科院分区：
文献类型：
--
作者：
H. Kilbinger;I. Wessler
在豚鼠回肠纵行肌间神经丛的制备过程中，比较了几种M受体激动剂对平滑肌(突触后效应)和乙酰胆碱释放(突触前效应)的影响。1.在释放实验中，用~3H-胆碱标记制剂中的乙酰胆碱储备物。在没有胆碱酯酶抑制剂的情况下，电场刺激引起氚的流出，这反映了~3H-乙酰胆碱的释放。激动剂奥曲莫林、槟榔碱、甲基呋喃甲醚、毒扁豆碱、卡巴胆碱、槟榔碱和匹罗卡品以浓度依赖的方式抑制刺激诱导的外流。在使用的最高浓度下，这些药物将诱发的流出抑制83-96%。东莨菪碱(10 Nm)可拮抗所有激动剂的抑制作用，提示外流的减少是由毒鼠碱受体介导的。2.氧化托莫林(100 Nm)抑制0.1 Hz场强刺激引起的抽动反应。这种抑制作用可被东莨菪碱(3 Nm)所克服。奥曲莫林的收缩抑制作用被认为是通过刺激突触前定位的M受体而产生的。3.所有激动剂都以浓度依赖的方式收缩纵肌。突触前效应和突触后效应的等级顺序不同。此外，效力比(以突触前和突触后的EC50衡量)并不是恒定的，而是在0.37(羟甲喋呤)到2.9(乙酰胆碱)之间变化。结果提示，纵行肌间神经丛突触前和突触后的M受体在药理性质上略有不同。
SummaryThe effects of several muscarinic agonists on smooth muscle (postsynaptic effect) and on acetylcholine release (presynaptic effect) were compared in the longitudinal muscle-myenteric plexus preparation of the guinea-pig ileum.1.For release experiments the acetylcholine stores of the preparation were labelled with 3H-choline. Electrical field stimulation in the absence of a cholinesterase inhibitor caused an outflow of tritium that reflected release of 3H-acetylcholine. The agonists oxotremorine, arecaidinepropargylester, methylfurmethide, muscarine, carbachol, arecoline and pilocarpine inhibited the stimulation-induced outflow in a concentration-dependent manner. At the highest concentrations used, the drugs depressed the evoked outflow by 83–96%. Scopolamine (10nM) antagonized the inhibitory effects of all agonists which suggests that the reduction of outflow was mediated by muscarine receptors.2.Oxotremorine (100nM) depressed the twitch response to field stimulation at 0.1 Hz. The inhibitory effect was overcome by scopolamine (3nM). The twitch-inhibitory effect of oxotremorine is thought to result from stimulation of presynaptically located muscarine receptors.3.All agonists contracted the longitudinal muscle in a concentration-dependent fashion. The rank orders of potencies for pre- and postsynaptic effects were dissimilar. Furthermore, the potency ratios (measured as EC 50 presynaptic: EC 50 postsynaptic) were not constant but varied from 0.37 (oxotremorine) to 2.9 (acetylcholine). The results suggest that pre-and postsynaptic muscarine receptors in the longitudinal muscle-myenteric plexus preparation differ slightly in their pharmacological properties.