EFFECTS OF PHLORIZIN AND SODIUM ON GLUCOSE-ELICITED ALTERATIONS OF CELL-JUNCTIONS IN INTESTINAL EPITHELIA
EFFECTS OF PHLORIZIN AND SODIUM ON GLUCOSE-ELICITED ALTERATIONS OF CELL-JUNCTIONS IN INTESTINAL EPITHELIA
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DOI：
10.1152/ajpcell.1990.258.1.c77
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发表时间：
1990-01-01
影响因子：
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通讯作者：
MADARA, JL
中科院分区：
文献类型：
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作者：
ATISOOK, K;CARLSON, S;MADARA, JL
葡萄糖改变吸收细胞紧密连接结构，并且根据阻抗分析模型推断，它会降低小肠中的紧密连接电阻（J. R. 帕彭海默，《膜生物学杂志》100：137 - 148，1987年；以及J. L. 马达拉和J. R. 帕彭海默，《膜生物学杂志》100：149 - 164，1987年）。在此，我们使用安装在尤斯灌流室中的黏膜片分析的常规方法，为这一假说提供进一步的证据。这种方法在研究潜在机制方面具有优势，包括离子和抑制剂对葡萄糖调节细胞间连接的影响。我们表明根皮苷阻断葡萄糖引起的电阻降低，并证明用胆碱替代钠也可阻止这种反应。伴随葡萄糖引发的这种反应而出现的吸收细胞紧密连接的扩张，同样可通过根皮苷处理或钠替代来阻止。根皮苷对连接通透性的影响在体内也能得到证实。根皮苷降低麻醉动物葡萄糖灌注肠道中肌酐的跨连接通量，即使考虑到根皮苷导致的液体吸收减少也是如此。最后，体内灌注研究表明，尽管在管腔葡萄糖浓度为25 mM时，几乎所有葡萄糖吸收都是跨细胞的，但在管腔葡萄糖浓度为125 mM时，由于溶剂拖拽穿过通透性改变的紧密连接，大约30%的葡萄糖吸收是通过细胞旁途径进行的。这些以及补充数据表明：1）肠道钠 - 葡萄糖协同转运蛋白的激活是引发事件，最终导致葡萄糖对吸收细胞紧密连接结构和功能的调节；2）通过常规的尤斯灌流室方法可以检测到葡萄糖对紧密连接功能的调节；3）即使是低浓度的管腔葡萄糖也能改变体内肠道中惰性溶质的清除；4）在高管腔葡萄糖浓度下，相当一部分净葡萄糖吸收可能通过改变后的紧密连接以细胞旁途径进行。
Glucose alters absorptive cell tight junction structure and, as deducted from an impedance analysis model, diminishes tight junction resistance in the small intestine (J. R. Pappenheimer, J. Membr. Biol. 100: 137-148, 1987; and J. L. Madara and J. R. Pappenheimer, J. Membr. Biol. 100: 149-164, 1987). Here we provide further evidence in support of this hypothesis using the conventional approach of analysis of mucosal sheets mounted in Ussing chambers. This approach offers advantages for investigating underlying mechanisms, including the effects of ions and inhibitors on the regulation of interecellular junctions by glucose. We show that phlorizin blocks a resistance decrease elicted by glucuse and demonstrate that substitution of choline for sodium also prevents the response. The dilatations in absorptive cell tight junctions that accompany this glucose-elcited response are similarly prevented by phlorizin exposure or sodium substitution. The effects of phlorizin on junctional permeability can also be demonstrated in vivo. Phlorizin reduces the transjunctional flux of creatinine in glucose-perfused intestines of anesthetized animals, even when account is taken of the reduction of fluid absorption caused by phlorizin. Last, in vivo perfusion studies suggest that although, at 25 mM luminal glucose, virtually all glucose absorption is transcellular, at a luminal glucose concentration of 125 mM .apprx. 30% of glucose absorption occurs paracellularly because of solvent drag across tight junctions of altered permeability. These and supplementary data indicate that 1) activation of the intestinal Na+-glucose cotransporter is the triggering event that eventuates in glucose-elicited regulation of absorptive cell tight junction structure and function, 2) glucose-elicited regulation of tight junction function can be detected by the conventional Ussing chamber approach, 3) even low concentrations of luminal glucose can alter clearance of inert solutes from the intestine in vivo, and 4) at high luminal glucose concentrations a substantial portion of net glucose absorption may occur paracellularly across altered tight junctions.