Izzo A A, Mascolo N, Di Carlo G, Capasso F
Department of Experimental Pharmacology, University of Naples Federico II, Italy.
Neuroscience. 1999;91(4):1575-80. doi: 10.1016/s0306-4522(98)00641-1.
The effect of muscarinic cholinoceptor antagonists was investigated on the ascending neural pathways activated by electrical stimulation in the guinea-pig ileum. For comparison, prejunctional and postjunctional effects of muscarinic cholinoceptor antagonists were also studied on circular smooth muscle. A two-compartment (oral and anal compartments) bath was used to study the ascending neural pathways. These were activated by electrical field stimulation in the anal compartment and the resulting contraction of the intestinal circular muscle in the oral compartment was recorded isotonically. Pirenzepine (10-300 nM), a muscarinic M1 cholinoceptor antagonist, reduced the ascending neural contractions in a concentration-dependent fashion when applied either to the oral or anal compartments (11-52% and 13-55% inhibition, respectively, P < 0.05). Pirenzepine inhibited (31+/-7%, P < 0.05) the acetylcholine (100 nM)-induced contractions at a higher non-selective concentration (300 nM), while its effect on the electrically-induced contractions was biphasic (10 and 30nM: 8-15% increase, P<0.05; 100 and 300 nM: 16-28% inhibition, P<0.05). The muscarinic M2 cholinoceptor antagonist methoctramine (3-100 nM) did not modify the contractions produced by 100 nM acetylcholine, electrically-induced contractions and the ascending neural contractions (when applied to either compartment). Parafluorohexahydrosiladifenidol (3-100 nM), a muscarinic M3 cholinoceptor antagonist, inhibited the contractions produced by 100 nM acetylcholine (19-81% and 15-69%), electrically-induced contractions (11-71% and 12-72%) and the ascending neural contractions (13-76% and 866%) when applied to the oral compartment, but it was without effect when applied to the anal compartment. These studies suggest that in the enteric ascending neural pathway, muscarinic M1 receptors are involved in neuroneuronal transmission, muscle contraction is mediated by muscarinic M3 cholinergic receptors, whereas muscarinic M2 receptors do not seem to participate.
研究了毒蕈碱型胆碱能受体拮抗剂对豚鼠回肠电刺激激活的上行神经通路的影响。为作比较，还研究了毒蕈碱型胆碱能受体拮抗剂对环行平滑肌的节前和节后效应。采用双室（口腔和肛门室）浴槽研究上行神经通路。在肛门室通过电场刺激激活这些通路，并等张记录口腔室肠环行肌产生的收缩。毒蕈碱M1胆碱能受体拮抗剂哌仑西平（10 - 300 nM），当应用于口腔或肛门室时，以浓度依赖性方式降低上行神经收缩（分别为11 - 52%和13 - 55%抑制，P < 0.05）。哌仑西平在较高的非选择性浓度（300 nM）时抑制（31±7%，P < 0.05）乙酰胆碱（100 nM）诱导的收缩，而其对电诱导收缩的作用是双相的（10和30 nM：增加8 - 15%，P < 0.05；100和300 nM：抑制16 - 28%，P < 0.05）。毒蕈碱M2胆碱能受体拮抗剂甲溴东莨菪碱（3 - 100 nM）不改变100 nM乙酰胆碱产生的收缩、电诱导收缩和上行神经收缩（当应用于任一室时）。毒蕈碱M3胆碱能受体拮抗剂对氟六氢硅二苯醇（3 - 100 nM），当应用于口腔室时，抑制100 nM乙酰胆碱产生的收缩（19 - 81%和15 - 69%）、电诱导收缩（11 - 71%和12 - 72%）和上行神经收缩（13 - 76%和866%），但应用于肛门室时无作用。这些研究表明，在肠上行神经通路中，毒蕈碱M1受体参与神经元间传递，肌肉收缩由毒蕈碱M3胆碱能受体介导，而毒蕈碱M2受体似乎不参与。
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