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去神经大鼠肠道平滑肌主动应激产生增加:毒蕈碱受体群体的功能分析

Increased active stress generation of denervated rat intestinal smooth muscle: functional analysis of muscarinic receptor population.

作者信息

Osinski M A, Bass P

机构信息

School of Pharmacy, University of Wisconsin-Madison.

出版信息

J Pharmacol Exp Ther. 1994 Mar;268(3):1368-73.

PMID:8138951
Abstract

The effects of denervation on the active stress production by the longitudinal muscle (LM) layer of rat jejunum were examined. Extrinsic and myenteric denervation of a segment of rat jejunum was accomplished by the serosal application of the cationic surfactant benzyldimethyltetradecylammonium chloride (BAC). Isolated muscle contraction experiments revealed that the LM of the jejunum taken from rats treated with BAC 15 days before developed significantly increased active stress in response to bethanechol and carbachol, but not in response to potassium chloride. No change in -log EC50 values of any of the agonists was observed in the denervated LM layer, although a significant increase in the slope of the carbachol and bethanechol concentration-response curves was observed in the denervated LM. Schild analysis of several muscarinic antagonists revealed a 3-fold increase in the apparent dissociation constant of the M2 antagonist methoctramine in BAC-treated LM. These results suggest that the increased responsiveness of the denervated LM may originate in the muscarinic receptor population of the myocytes.

摘要

研究了去神经对大鼠空肠纵肌(LM)层主动张力产生的影响。通过在大鼠空肠段浆膜表面应用阳离子表面活性剂苄基二甲基十四烷基氯化铵(BAC)实现空肠的外在和肌间神经去神经支配。离体肌肉收缩实验显示,在BAC处理15天前的大鼠所取空肠LM,对氨甲酰甲胆碱和卡巴胆碱产生的主动张力显著增加,但对氯化钾无反应。去神经支配的LM层中,任何激动剂的-log EC50值均未观察到变化,尽管在去神经支配的LM中观察到卡巴胆碱和氨甲酰甲胆碱浓度-反应曲线斜率显著增加。对几种毒蕈碱拮抗剂的Schild分析显示,在BAC处理的LM中,M2拮抗剂甲氧基氨甲酰胆碱的表观解离常数增加了3倍。这些结果表明,去神经支配的LM反应性增加可能源于肌细胞的毒蕈碱受体群体。

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Increased active stress generation of denervated rat intestinal smooth muscle: functional analysis of muscarinic receptor population.去神经大鼠肠道平滑肌主动应激产生增加:毒蕈碱受体群体的功能分析
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