Effect of E-coli heat-stable enterotoxin on colonic transport in guanylyl cyclase C receptor-deficient mice

Effect of E-coli heat-stable enterotoxin on colonic transport in guanylyl cyclase C receptor-deficient mice
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DOI:
10.1152/ajpgi.2001.280.2.g216
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发表时间:
2001-02-01
影响因子:
4.5
通讯作者:
Giannella, RA
Giannella, RA
中科院分区:
医学2区
文献类型:
--
作者:
Charney, AN;Egnor, RW;Giannella, RA

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我们研究了结肠鸟苷酸环化酶C(GCC)受体在GCC受体缺陷小鼠中的功能重要性。用戊巴比妥钠麻醉小鼠,并在短路条件下在HCO 3- Ringer中的Ussing室中研究结肠段。受体缺陷小鼠近端结肠表现出类似的净Na+吸收,较低的净Cl-吸收,和一个负的残余离子通量(JR),表明净HCO 3-吸收与正常小鼠相比。在正常小鼠近端结肠中,粘膜添加50 nM大肠杆菌热稳定肠毒素(STa)增加了Cl-(J(s-->m)(Cl)Cl)的浆膜-粘膜通量,并降低了净Cl-通量(J(net)(Cl)),同时增加了短路电流(Isc)、电位差(PD)和组织电导(G)。Sercostostosta没有效果。在远端结肠既不粘膜也不serumSTa影响离子转运。在受体缺陷的小鼠,无论是粘膜,也不是seruminos 500 nM STa影响电解质转运在近端或远端结肠。在这些小鼠中,1 mM 8-溴-cGMP在近端结肠J(s->m)(Cl)和J(net)(Cl)、I-sc、PD、G和J(R)中产生类似于正常小鼠中粘膜STa添加的变化。我们的结论是GCC受体是必要的,在小鼠近端结肠粘膜STa的分泌反应。
We studied the functional importance of the colonic guanylyl cyclase C (GCC) receptor in GCC receptor-deficient mice. Mice were anesthetized with pentobarbital sodium, and colon segments were studied in Ussing chambers in HCO3- Ringer under short-circuit conditions. Receptor-deficient mouse proximal colon exhibited similar net Na+ absorption, lower net Cl- absorption, and a negative residual ion flux (JR), indicating net HCO3- absorption compared with that in normal mice. In normal mouse proximal colon, mucosal addition of 50 nM Escherichia coli heat-stable enterotoxin (STa) increased the serosal-to-mucosal flux of Cl- (J(s-->m)(Cl) Cl) and decreased net Cl- flux (J(net)(Cl)) accompanied by increases in short-circuit current (Isc), potential difference (PD), and tissue conductance (G). Serosal STa had no effect. In distal colon neither mucosal nor serosal STa affected ion transport. In receptor-deficient mice, neither mucosal nor serosal 500 nM STa affected electrolyte transport in proximal or distal colon. In these mice, 1 mM 8-bromo-cGMP produced changes in proximal colon J(s-->m)(Cl) and J(net)(Cl), I-sc, PD, G, and J(R) similar to mucosal STa addition in normal mice. We conclude that the GCC receptor is necessary in the mouse proximal colon for a secretory response to mucosal STa.