Du Zhaopeng, Ferguson William, Wang Tong
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520-8026, USA.
Am J Physiol Renal Physiol. 2003 Apr;284(4):F688-92. doi: 10.1152/ajprenal.00261.2002. Epub 2003 Jan 14.
It has been well documented that low concentrations of ANG II (10(-11) to 10(-10) M) stimulate, whereas high concentrations of ANG II (10(-8) to 10(-5) M) inhibit Na(+) transport in proximal tubules of rat and rabbit kidneys. Measured ANG II concentration in proximal tubular fluid is in the nanomolar range. In the present study, we investigated the role of PKC, intracellular Ca(2+), and cAMP in modulating the effects of luminal ANG II on Na(+) absorption by microperfusion techniques in rabbit superficial segment of proximal tubules in vitro. We confirmed that ANG II (10(-9) M) had no change on fluid absorption (J(v)); however, fluid absorption increased significantly when 10(-9) M ANG II and 3,4,5-trimethoxybenzoic acid-8-(diethylamino)octyl ester (TMB-8), a blocker of intracellular calcium mobilization, were added together. In contrast, ANG II significantly decreased J(v) when PKC was inhibited. When 10(-9) M ANG II was present together with 1-(5-isoquinolinesulfonyl)-2-mehtylpiperazine and TMB-8, no significant change of J(v) occurred. Inhibition of endogenous cAMP activity by a PKA inhibitor did not change either basal or ANG II-stimulated fluid absorption. Our results indicate that ANG II regulates Na(+) absorption by a cAMP-independent mechanism and that PKC and intracellular calcium both play a critical role in modulating the effects of physiological concentration of ANG II on proximal tubule transport. Balance between these two cytosolic messengers modulates the effects of ANG II on fluid absorption in the proximal tubule.
有充分的文献记载，低浓度的血管紧张素II（10^(-11)至10^(-10)M）具有刺激作用，而高浓度的血管紧张素II（10^(-8)至10^(-5)M）则抑制大鼠和兔肾脏近端小管中的钠转运。在近端小管液中测得的血管紧张素II浓度处于纳摩尔范围内。在本研究中，我们通过体外微灌注技术，研究了蛋白激酶C（PKC）、细胞内钙离子和环磷酸腺苷（cAMP）在调节管腔血管紧张素II对兔近端小管浅表节段钠吸收的作用中的作用。我们证实，血管紧张素II（10^(-9)M）对液体吸收（J(v)）没有影响；然而，当加入10^(-9)M血管紧张素II和细胞内钙动员阻滞剂3,4,5-三甲氧基苯甲酸-8-（二乙氨基）辛酯（TMB-8）时，液体吸收显著增加。相反，当PKC受到抑制时，血管紧张素II显著降低J(v)。当10^(-9)M血管紧张素II与1-（5-异喹啉磺酰基）-2-甲基哌嗪和TMB-8同时存在时，J(v)没有显著变化。蛋白激酶A（PKA）抑制剂对内源性cAMP活性的抑制既不改变基础液体吸收，也不改变血管紧张素II刺激的液体吸收。我们的结果表明，血管紧张素II通过一种不依赖cAMP的机制调节钠吸收，并且PKC和细胞内钙在调节生理浓度的血管紧张素II对近端小管转运的作用中都起着关键作用。这两种胞质信使之间的平衡调节血管紧张素II对近端小管液体吸收的作用。
