Cellular mechanisms of hormone and drug interaction in ion transport in the nephron

（1）CS-045（曲格列酮）的肾脏结核作用：CS-045已被开发用于耐胰岛素的糖尿病多发性硬化症的治疗。反应的机制被认为是对胰岛素受体的敏感性比对胰岛素释放的刺激性更敏感。为了通过该代理引起的修饰作为一个侧面效应来激发机制，我们研究了在兔正直管（PST）上完全填充的CS-045的直接作用。通过测量电子物理学参数表示HCO-D23-D2-conductance in the basolateral membrane and Na-3 HC 0-D23-co-transporter activity as determined in contracellular pH（pHi），我们演示CS-045直接刺激Na-3 HC 0-D23-co-transporter activity in the basolateral membrane in the basolateral membrane in a dose-dependent mans，导致PST中的钠再吸收中的增加。这将是，至少在部分中，对CS-045捕获的edema负有责任。（2） Renal tubular function of receptor/transporter knockout mice： We established clearance technique to examine renal function of PGE2-knockout mice。在用五溴二苯醚、恒定IV输液的情况下，老鼠是从尾纹制成的。尿液体积、质量和Nawere对收集的样本进行了测量。PGE 2导致在他控制的老鼠中尿体积和钠提取，但不在PGE 2受体knockout老鼠中。我们成功地从P-糖蛋白质肾脏（P-gp） knockout老鼠中完全孤立的PST。由于内源性罗丹氟灭绝的减少，P-gp的运输活动被估计表明，P-gp对于从PST的表皮膜中提取药物是关键的，通过机制与控制老鼠中激活PKC和P1-3激酶的机制进行链接，但P-gp knockout老鼠错过了这一功能。

(1) Renal tubular action of CS-045(troglitazone): CS-045 has been developed for the treatment of insulin resistant diabetes mellitus. The mechanism of action is assumed to be sensitization of insulin receptor rather than stimulation of insulin release. To elucidate the mechanisms by which this agent causes edema as a side-effect, we examined direct action of CS-045 on the rabbit proximal straight tubule (PST) perfused in vitro. By measuring the electrophysiological parameters representing HCOィイD23ィエD2-conductance in the basolateral membrane and Na-3HC0ィイD23ィエD2 co-transporter activity as determined by changes in intracellular pH(pHi), we demonstrated that CS-045 directly stimulates Na-3HC0ィイD23ィエD2 co-transporter activity in the basolateral membrane in a dose-dependent manner, leading to an increase in Na reabsorption in the PST. This would, at least in part, be responsible for edema caused by CS-045.(2) Renal tubular function of receptor/transporter knockout mice: We established clearance technique to examine renal function of PGE2-knockout mice. In mice anesthetized with pentobarbital, constant iv infusion was performed from tail vein. Urine volume, osmolality and Na were measured on samples collected from the bladder. PGE2 caused significant increase in urine volume and Na excretion in he control mice, but not in the PGE2-recptor knockout mice. We succeeded to perfuse isolated PST from the kidney of P-glycoprotein (P-gp) knockout mice. From the decrement of intracellular rodamin fluorescence, transport activity of P-gp was estimated It was shown that P-gp is critical for drug excretion from the apical membrane of PST by acting through mechanisms linking with activation of PKC and P1-3 kinase in the control mice, but that P-gp knockout mice lack this function.