ATP is released from guinea pig ureter epithelium on distension
ATP is released from guinea pig ureter epithelium on distension
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DOI：
10.1152/ajprenal.00293.2000
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发表时间：
2002-02-01
影响因子：
4.2
通讯作者：
Burnstock, G
中科院分区：
文献类型：
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作者：
Knight, GE;Bodin, P;Burnstock, G
在 20 至 700 cmH(2)O 的压力下，灌注豚鼠输尿管扩张，以压力依赖性方式增加从上皮释放的 ATP 量。基础灌注（40μl/min）期间，灌注液含有10pmol/ml ATP；在不同的膨胀压力下，该值增加了 10 至 50 倍。 ATP 在扩张过程中从上皮细胞中释放出来，因为机械去除尿路上皮会阻止释放。灌注液中未检测到乳酸脱氢酶，扫描电子显微镜证实扩张后尿路上皮完整。由于拉伸激活通道的激活，ATP 未释放，因为钆 (10 muM) 无法影响 ATP 释放。格列本脲 (10 muM) 已知可抑制 ATP 结合盒 (ABC) 蛋白家族的两个成员，但不影响扩张后 ATP 的释放；维拉帕米（10 μM）也没有。相比之下，干扰囊泡形成或运输的莫能菌素 (100 μM) 和布雷菲德菌素 A (10 μM) 均抑制扩张诱发的 ATP 释放，而这种释放是 Ca2+ 依赖性的。这表明输尿管上皮释放 ATP 可能是由囊泡胞吐作用介导的。中空内脏器官扩张释放的 ATP 的作用与嘌呤能机械感觉转导的概念相关，特别涉及伤害感受和上皮下感觉神经上 P2X(3) 受体的激活。
Distension of the perfused guinea pig ureter at pressures from 20 to 700 cmH(2)O increased the amount of ATP released from the epithelium in a pressure-dependent manner. During basal perfusion (40 mul/min), the perfusate contained 10 pmol/ml ATP; this increased 10- to 50-fold at various distending pressures. ATP was released from epithelial cells during distension as mechanical removal of the urothelium blocked release. No lactate dehydrogenase was detected in the perfusate, and scanning electron microscopy confirmed an intact urothelium after distension. ATP was not released due to the activation of stretch-activated channels, as gadolinium (10 muM) failed to affect ATP release. Glibenclamide (10 muM), known to inhibit two members of the ATP-binding cassette (ABC) protein family, did not affect ATP release after distension; nor did verapamil (10 muM). In contrast, both monensin (100 muM) and brefeldin A (10 muM), which interfere with vesicular formation or trafficking, inhibited distension-evoked ATP release, which was Ca2+-dependent. This suggests that ATP release from the ureter epithelium might be mediated by vesicular exocytosis. The role of ATP released by distension of hollow visceral organs is discussed in relation to the concept of purinergic mechanosensory transductions, with special reference to nociception and the activation of P2X(3) receptors on the subepithelial sensory nerves.