Charney A N, Egnor R W, Alexander-Chacko J T, Zaharia V, Mann E A, Giannella R A
Nephrology Section, Veterans Affairs Medical Center, 423 E. 23rd Street, New York, NY 10010, USA.
Am J Physiol Gastrointest Liver Physiol. 2001 Feb;280(2):G216-21. doi: 10.1152/ajpgi.2001.280.2.G216.
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 (J(R)), 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)) and decreased net Cl- flux (J(net)(Cl)) accompanied by increases in short-circuit current (I(sc)), 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.
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，并在短路条件下于含有HCO3-的林格氏液中，在尤斯灌流小室中研究结肠段。受体缺陷小鼠的近端结肠表现出相似的净Na+吸收、较低的净Cl-吸收以及负的残余离子通量（J(R)），表明与正常小鼠相比有净HCO3-吸收。在正常小鼠近端结肠中，黏膜添加50 nM大肠杆菌热稳定肠毒素（STa）可增加Cl-的浆膜到黏膜通量（J(s-->m)(Cl)）并降低净Cl-通量（J(net)(Cl)），同时短路电流（I(sc)）、电位差（PD）和组织电导（G）增加。浆膜添加STa则无影响。在远端结肠，黏膜和浆膜添加STa均不影响离子转运。在受体缺陷小鼠中，黏膜和浆膜添加500 nM STa均不影响近端或远端结肠的电解质转运。在这些小鼠中，1 mM 8-溴-cGMP引起近端结肠J(s-->m)(Cl)、J(net)(Cl)、I(sc)、PD、G和J(R)的变化，类似于正常小鼠黏膜添加STa后的变化。我们得出结论，GCC受体在小鼠近端结肠中对于对黏膜STa的分泌反应是必需的。
