豚鼠回肠节前毒蕈碱（M1）受体相互作用：西沙必利无作用

Prejunctional muscarinic (M1)-receptor interactions on guinea-pig ileum: lack of effect of cisapride.

作者信息

Schuurkes J A, Van Bergen P J, Van Nueten J M

机构信息

Department of Pharmacodynamics, Janssen Research Foundation, Beerse, Belgium.

出版信息

Br J Pharmacol. 1988 May;94(1):228-34. doi: 10.1111/j.1476-5381.1988.tb11519.x.

DOI:10.1111/j.1476-5381.1988.tb11519.x

PMID:2456809

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1853913/

Abstract

UNLABELLED

Cisapride stimulates gastrointestinal motility, probably by enhancing the release of acetylcholine from myenteric nerve endings. Such an effect could be mediated via presynaptic muscarinic (M1)-receptors. Our aim was to determine whether cisapride could antagonize the inhibitory effects of a M1-agonist, McN-A-343 or mimic the effects of a M1-antagonist, pirenzepine. 2. Longitudinal segments were suspended in Krebs solution (95% O2, 5% CO2, 37.5 degrees C) for isometric tension recording (preload 1 g) during electrical transmural stimulation (0.1 Hz, 1 ms, sub- or supramaximal current). 3. McN-A-343 (2.0 x 10(-6) M) reduced the contractile response to supramaximal stimulation (EC50 = 1.6 x 10(-6) M), but had no effect on the contractions induced by exogenous acetylcholine. 4. The inhibitory effect of McN-A-343 on the contractile response to electrical stimulation could be reversed by pirenzepine (EC50 = 1.6 x 10(-8) M) but not by atropine. At these concentrations pirenzepine itself did not modify the contractile response to electrical stimulation. However, at 50 times higher concentrations pirenzepine inhibited the response to electrical stimulation as well as the response to exogenous acetylcholine (EC50 = 8.5 x 10(-7) M). 5. Cisapride enhanced the contractile response to submaximal electrical stimulation by 49 +/- 10%. This stimulating effect of cisapride was not affected by the presence of pirenzepine but was reduced in the presence of McN-A-343 (22 +/- 7%). 6.

IN CONCLUSION

the effects of McN-A-343 and pirenzepine on the electrically stimulated guinea-pig ileum are compatible with an interaction on presynaptic muscarinic-(M1)-receptors. Cisapride enhances the twitch amplitude via mechanisms independent of such M1-receptor interactions.

摘要

未标记

西沙必利可能通过增强肠肌间神经末梢乙酰胆碱的释放来刺激胃肠蠕动。这种作用可能通过突触前毒蕈碱（M1）受体介导。我们的目的是确定西沙必利是否能拮抗M1激动剂 McN - A - 343的抑制作用，或模拟M1拮抗剂哌仑西平的作用。2. 将纵向肠段悬挂于 Krebs 溶液（95% O₂，5% CO₂，37.5℃）中，在经壁电刺激（0.1 Hz，1 ms，亚最大或最大电流）期间进行等长张力记录（预负荷1 g）。3. McN - A - 343（2.0×10⁻⁶ M）降低了对最大刺激的收缩反应（EC₅₀ = 1.6×10⁻⁶ M），但对外源性乙酰胆碱诱导的收缩无影响。4. McN - A - 343对电刺激收缩反应的抑制作用可被哌仑西平（EC₅₀ = 1.6×10⁻⁸ M）逆转，但不能被阿托品逆转。在这些浓度下，哌仑西平本身不改变对电刺激的收缩反应。然而，在高50倍的浓度下，哌仑西平抑制对电刺激的反应以及对外源性乙酰胆碱的反应（EC₅₀ = 8.5×10⁻⁷ M）。5. 西沙必利使对亚最大电刺激的收缩反应增强了49±10%。西沙必利的这种刺激作用不受哌仑西平存在的影响，但在 McN - A - 343存在时减弱（22±7%）。6.