Lipkowitz M S, London R D, Beck J C, Abramson R G
Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029.
Am J Physiol. 1992 Jul;263(1 Pt 2):F144-51. doi: 10.1152/ajprenal.1992.263.1.F144.
The effects on ionic permeability of toxins and hormones that activate or deactivate the guanine nucleotide regulatory (G) proteins that govern adenylate cyclase activity were examined in rat renal proximal tubule cell brush-border membranes. These studies demonstrate that activation of stimulatory G (Gs) proteins by cholera toxin or parathyroid hormone and deactivation of inhibitory (G (Gi) proteins by pertussis toxin result in a selective increase in Cl- permeability relative to that of K+ as determined with the potential-sensitive fluorescent probe 3,3'-dipropylthiadicarbocyanine iodide [diS-C3-(5)]. In contrast, activation of Gi by angiotensin II significantly decreases relative Cl- permeability. The selective increase in relative Cl- permeability induced by parathyroid hormone results in an inside-negative potential in membrane vesicles exposed to an inward NaCl gradient that is of sufficient magnitude to stimulate electrogenic, Na(+)-dependent glucose transport. These data suggest that the relative ionic permeabilities of brush-border membranes are tonically regulated by the opposing effects of hormones that act via Gs or Gi proteins. Changes in membrane potential resulting from this regulation may play an important role in modifying transport in the proximal tubule.
在大鼠肾近端小管细胞刷状缘膜中，研究了激活或失活调节腺苷酸环化酶活性的鸟嘌呤核苷酸调节（G）蛋白的毒素和激素对离子通透性的影响。这些研究表明，霍乱毒素或甲状旁腺激素激活刺激性G（Gs）蛋白，百日咳毒素使抑制性G（Gi）蛋白失活，导致相对于K+而言，Cl-通透性选择性增加，这是用电压敏感荧光探针3,3'-二丙基硫代二羰花青碘化物[diS-C3-(5)]测定的。相反，血管紧张素II激活Gi会显著降低相对Cl-通透性。甲状旁腺激素诱导的相对Cl-通透性选择性增加，会导致暴露于内向NaCl梯度的膜囊泡中出现内负电位，该电位足以刺激电驱动的、依赖Na+的葡萄糖转运。这些数据表明，刷状缘膜的相对离子通透性受到通过Gs或Gi蛋白起作用的激素的相反作用的紧张性调节。这种调节引起的膜电位变化可能在近端小管转运调节中起重要作用。
