Wang T, Chan Y L
Department of Physiology and Biophysics, University of Illinois, College of Medicine, Chicago 60612.
J Membr Biol. 1990 Aug;117(2):131-9. doi: 10.1007/BF01868680.
Activation of protein kinase C has been shown to cause both stimulation and inhibition of transport processes in the brush-border membrane and renal tubule. This study was designed to examine the dose-response nature and time-dependent effect of 4 beta-phorbol-12-myristate-13-acetate (PMA) on the rates of bicarbonate absorption (JHCO3) and fluid absorption (Jv) in the proximal convoluted tubule (PCT) of rat kidney. Bicarbonate flux was determined by total CO2 changes between the collected fluid and the original perfusate as analyzed by microcalorimetry. Luminal perfusion of PMA (10(-10) approximately 10(-5) M) within 10 min caused a significant increase of JHCO3 and Jv. A peaked curve of the dose response was observed with maximal effect at 10(-8) M PMA on both bicarbonate and fluid reabsorption, which could be blocked completely by amiloride (10(3) M) and EIPA (10(-5) M). On the other hand, with an increase of perfusion time beyond 15 min. PMA (10(-8) and 10(-6) M) could inhibit JHCO3 and Jv. Amiloride (10(-3) M) or EIPA (10(-5) M) significantly inhibits JHCO3 and Jv, while there is no additive effect of PMA and amiloride or EIPA on PCT transport. An inactive phorbol-ester, 4 alpha-phorbol, that does not activate protein kinase C, had no effects on JHCO3 and Jv. Capillary perfusion of PMA (10(-8) M) significantly stimulate both JHCO3 and Jv; however, PMA did not affect glucose transport from either the luminal side or basolateral side of the PCT. These results indicate that activation of endogenous protein kinase C by PMA could either stimulate or inhibit both bicarbonate and fluid reabsorption in the PCT dependent on time and dose, and these effects are through the modulation of Na+/H+ exchange mechanism.
蛋白激酶C的激活已被证明可引起刷状缘膜和肾小管中转运过程的刺激和抑制。本研究旨在研究4β-佛波醇-12-肉豆蔻酸酯-13-乙酸酯（PMA）对大鼠肾近端曲管（PCT）中碳酸氢盐吸收速率（JHCO3）和液体吸收速率（Jv）的剂量反应特性和时间依赖性效应。通过微量量热法分析收集的液体与原始灌流液之间的总CO2变化来确定碳酸氢盐通量。在10分钟内管腔灌注PMA（10(-10)约10(-5)M）导致JHCO3和Jv显著增加。观察到剂量反应的峰值曲线，在10(-8)M PMA时对碳酸氢盐和液体重吸收均有最大效应，这可被氨氯地平（10(3)M）和EIPA（10(-5)M）完全阻断。另一方面，随着灌注时间超过15分钟增加。PMA（10(-8)和10(-6)M）可抑制JHCO3和Jv。氨氯地平（10(-3)M）或EIPA（10(-5)M）显著抑制JHCO3和Jv，而PMA与氨氯地平或EIPA对PCT转运无相加作用。一种不激活蛋白激酶C的无活性佛波酯4α-佛波醇对JHCO3和Jv无影响。PMA（10(-8)M）的毛细血管灌注显著刺激JHCO3和Jv；然而，PMA不影响PCT管腔侧或基底外侧的葡萄糖转运。这些结果表明，PMA激活内源性蛋白激酶C可根据时间和剂量刺激或抑制PCT中的碳酸氢盐和液体重吸收，并且这些效应是通过调节Na+/H+交换机制实现的。
