Lorenzen M, Frindt G, Taylor A, Windhager E E
Am J Physiol. 1987 Jun;252(6 Pt 2):F1103-11. doi: 10.1152/ajprenal.1987.252.6.F1103.
Quinidine, a compound thought to increase cytosolic calcium ion activity, has been found to inhibit the hydrosmotic response to vasopressin (VP) and adenosine 3',5'-cyclic monophosphate (cAMP) in the toad urinary bladder. To test whether this drug has a similar action in the mammalian nephron, the effect of quinidine on the hydraulic conductivity of the isolated perfused rabbit cortical collecting tubule (CCT) exposed to either 20 microU/ml VP or 10(-4) M 8-(p-chlorophenylthio) - adenosine 3',5' - cyclic monophosphate (8-CPT-cAMP) was studied. Quinidine had no effect on the basal water permeability of the CCT. Quinidine sulfate (10(-4) M) reduced the VP-stimulated water permeability from 280 +/- 50 X 10(-7) to 115 +/- 41 X 10(-7) cm X s-1 X atm-1 (P less than 0.05). The hydrosmotic response to 8-CPTcAMP was likewise reduced following exposure to quinidine. This effect was shown to be dose dependent. In paired experiments, inhibition of the response to 10(-4) M 8-CPTcAMP averaged 11% at 10(-6) M, 27% at 5 X 10(-6) M, 53% at 5 X 10(-5) M, and 50% at 10(-4) M quinidine. Inhibition of the response to 8-CPTcAMP was estimated to be half maximal at approximately 5 X 10(-6) M quinidine. Tubules were protected against the quinidine-induced inhibition by the addition of 6.5 X 10(-5) M quin 2-acetoxymethylester in the presence of low peritubular Ca concentration. These results are consistent with the view that elevated cytosolic Ca ion levels inhibit the increase in water permeability elicited by VP or exogenous cAMP in the mammalian CCT.
奎尼丁是一种被认为可增加胞质钙离子活性的化合物，现已发现它能抑制蟾蜍膀胱对血管加压素（VP）和3',5'-环磷酸腺苷（cAMP）的渗透反应。为了测试这种药物在哺乳动物肾单位中是否有类似作用，研究了奎尼丁对暴露于20微单位/毫升VP或10⁻⁴ M 8-（对氯苯硫基）-3',5'-环磷酸腺苷（8-CPT-cAMP）的离体灌注兔皮质集合小管（CCT）水导率的影响。奎尼丁对CCT的基础水通透性没有影响。硫酸奎尼丁（10⁻⁴ M）使VP刺激的水通透性从280±50×10⁻⁷降至115±41×10⁻⁷厘米×秒⁻¹×大气压⁻¹（P＜0.05）。暴露于奎尼丁后，对8-CPTcAMP的渗透反应同样降低。这种作用呈剂量依赖性。在配对实验中，对10⁻⁴ M 8-CPTcAMP反应的抑制在10⁻⁶ M奎尼丁时平均为11%，在5×10⁻⁶ M时为27%，在5×10⁻⁵ M时为53%，在10⁻⁴ M奎尼丁时为50%。估计在约5×10⁻⁶ M奎尼丁时对8-CPTcAMP反应的抑制达到半数最大效应。在低肾小管周围钙浓度存在的情况下，加入6.5×10⁻⁵ M喹尼丁-2-乙酰氧甲酯可保护小管免受奎尼丁诱导的抑制。这些结果与以下观点一致，即胞质钙离子水平升高会抑制哺乳动物CCT中由VP或外源性cAMP引起的水通透性增加。
