Pannexin 1 channels play essential roles in urothelial mechanotransduction and intercellular signaling.
Pannexin 1 channels play essential roles in urothelial mechanotransduction and intercellular signaling.
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DOI：
10.1371/journal.pone.0106269
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Suadicani SO
中科院分区：
文献类型：
--
作者：
Negoro H;Urban-Maldonado M;Liou LS;Spray DC;Thi MM;Suadicani SO
尿路上皮细胞通过释放ATP来响应膀胱扩张，而膀胱内以及从膀胱到中枢神经系统的ATP信号传导对于正常的膀胱功能至关重要。在其他细胞类型中，泛连接蛋白1（Panx 1）通道通过与P2 X7受体（P2 X7 Rs）相互作用为机械诱导的ATP流出和ATP诱导的ATP释放提供途径。我们报告说，Panx 1和P2 X7 R的功能表达在膀胱粘膜和永生化的人尿路上皮细胞（TRT-HU 1），并参与尿路上皮ATP的释放和信号。Panx 1通道阻断剂甲氟喹（MFQ）减少了由扩张引起的离体大鼠膀胱ATP释放，并在缺乏Panx 1或P2 X7 R表达的小鼠中减弱。MFQ和P2 X7 R阻断剂A438079在TRT-HU 1细胞中抑制低渗休克诱导的YoPro染料摄取，并且在来自缺乏Panx 1或P2 X7 R表达的小鼠的原代尿路上皮细胞中也被钝化。冲洗诱导的TRT-HU 1细胞的机械刺激触发ATP释放，这是减少MFQ和加强在低二价阳离子溶液（LDPBS），一种已知的条件，以增强P2 X7 R激活。在LDPBS中，以细胞间Ca 2+波半径评估的ATP信号传导显著较大，MFQ和腺苷三磷酸双磷酸酶（ATP清除剂）降低。这些发现表明Panx 1通过为机械诱导的ATP释放提供直接途径并通过与P2 X7 Rs功能性相互作用参与尿路上皮机械转导和信号传导。
Urothelial cells respond to bladder distension with ATP release, and ATP signaling within the bladder and from the bladder to the CNS is essential for proper bladder function. In other cell types, pannexin 1 (Panx1) channels provide a pathway for mechanically-induced ATP efflux and for ATP-induced ATP release through interaction with P2X7 receptors (P2X7Rs). We report that Panx1 and P2X7R are functionally expressed in the bladder mucosa and in immortalized human urothelial cells (TRT-HU1), and participate in urothelial ATP release and signaling. ATP release from isolated rat bladders induced by distention was reduced by the Panx1 channel blocker mefloquine (MFQ) and was blunted in mice lacking Panx1 or P2X7R expression. Hypoosmotic shock induced YoPro dye uptake was inhibited by MFQ and the P2X7R blocker A438079 in TRT-HU1 cells, and was also blunted in primary urothelial cells derived from mice lacking Panx1 or P2X7R expression. Rinsing-induced mechanical stimulation of TRT-HU1 cells triggered ATP release, which was reduced by MFQ and potentiated in low divalent cation solution (LDPBS), a condition known to enhance P2X7R activation. ATP signaling evaluated as intercellular Ca2+ wave radius was significantly larger in LDPBS, reduced by MFQ and by apyrase (ATP scavenger). These findings indicate that Panx1 participates in urothelial mechanotransduction and signaling by providing a direct pathway for mechanically-induced ATP release and by functionally interacting with P2X7Rs.
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影响因子：
2.1
作者：
Du, Shuqi;Araki, Isao;Takeda, Masayuki
通讯作者：
Takeda, Masayuki
影响因子：
5.5
作者：
Ferguson, DR;Kennedy, I;Burton, TJ
通讯作者：
Burton, TJ
DOI：
10.1073/pnas.0611280104
发表时间：
2007-04-10
影响因子：
11.1
作者：
Huang, Yi-Jen;Maruyama, Yutaka;Roper, Stephen D.
通讯作者：
Roper, Stephen D.
DOI：
10.1152/ajprenal.00321.2006
发表时间：
2008-04-01
影响因子：
4.2
作者：
Chopra, Bikramjit;Gever, Joel;Birder, Lori A.
通讯作者：
Birder, Lori A.
影响因子：
5.8
作者：
Alexandrina Timoteo, M.;Carneiro, Ines;Correia-de-Sa, Paulo
通讯作者：
Correia-de-Sa, Paulo