Receptors and mechanisms mediating the biphasic response evoked by bradykinin in rat colonic smooth muscle

Receptors and mechanisms mediating the biphasic response evoked by bradykinin in rat colonic smooth muscle
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介导大鼠结肠平滑肌缓激肽引起的双相反应的受体和机制

DOI:
10.1111/nmo.12165
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发表时间:
2013
影响因子:
3.5
通讯作者:
Diener M
Diener M
中科院分区:
医学3区
文献类型:
--
作者:
Würner L;Diener M

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在大鼠的十二指肠中,缓激肽会引起先松弛后收缩。不同类型的离子通道和受体以及非肌肉细胞被认为参与了这种反应。由于尚不清楚这些变化是否也在大鼠大肠中观察到,以及这种反应的机制可能是什么,因此我们测试了缓激肽对大鼠结肠运动的影响。方法测量全层或各层剥离后的薄片的收缩量。采用免疫组织化学和RT - PCR分析缓激肽受体的表达。用钙离子成像技术研究分离的肠肌细胞。关键结果缓激肽引起大鼠结肠双相收缩反应(先松弛后收缩),对河豚毒素具有抗性。激肽诱导的松弛被四戊基氯化铵(一种Ca2+激活的K+通道阻滞剂)所抑制。Des - arg9 - bradykinin对天然结肠没有任何影响,尽管在体外预孵育5 h后,这种b1受体激动剂引起了收缩反应。与对照刺激相比,连续消融肠壁粘附层大大降低了对缓激肽的反应,即甲氨基酚,这表明非肌肉细胞在这种反应的调解中起作用。结论与推论:缓激肽可引起大鼠结肠收缩性的双期变化。在天然肠道中,只有b2受体参与了这种作用。邻近细胞明显使平滑肌对这些受体的刺激敏感。
BackgroundIn rat duodenum, bradykinin induces a relaxation followed by a contraction. Different types of ion channels and receptors as well as non‐muscle cells have been suggested to be involved in this response. As it is unclear whether these changes are observed also in rat large intestine and the mechanisms which might underlie this response, the effect of bradykinin on rat colonic motility was tested.MethodsIsometric contractions were measured on full‐thickness preparations or preparations, from which individual layers had been dissected. The expression of bradykinin receptors was analyzed by immunohistochemistry and RT‐PCR. Isolated intestinal muscle cells were investigated with Ca2+‐imaging techniques.Key ResultsBradykinin caused a biphasic contractile response (initial relaxation followed by contraction) in rat colon, which was resistant against tetrodotoxin. The kinin‐induced relaxation was inhibited by tetrapentylammonium chloride, a blocker of Ca2+‐activated K+channels. Des‐arg9‐bradykinin did not induce any effect on the native colon, although after 5 hin vitropreincubation, a contractile response was evoked by this B1receptor agonist. The consecutive ablation of adherent layers of the intestinal wall strongly reduced the response to bradykinin in comparison with a control stimulus, i.e., carbachol, suggesting a contribution of non‐muscle cells in the mediation of this response.Conclusions & InferencesBradykinin induced a biphasic change in contractility in the rat colon. In the native intestine, only the B2receptor is involved in this effect. Neighboring cell obviously sensitize the smooth muscle to the stimulation of these receptors.
地塞米松和蛋白激酶 C 抑制剂对离体大鼠回肠中缓激肽 B1 mRNA 诱导和缓激肽 B1 受体介导的收缩反应的影响。
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