Yao Lijun, Huang Dan-Yang, Pfaff Imke L, Nie Xin, Leitges Michael, Vallon Volker
Institute of Pharmacology and Toxicology, University of Tübingen, 72074 Tuebingen, Germany.
Am J Physiol Renal Physiol. 2004 Aug;287(2):F299-304. doi: 10.1152/ajprenal.00274.2003. Epub 2004 Mar 23.
In mouse kidney, the conventional protein kinase C (PKC) isoenzyme alpha is expressed in glomeruli, the cortical collecting duct (intercalated cells only), and medullary collecting duct. To get insights on its function, PKC-alpha knockout (-/-) and wild-type (+/+) mice were studied. When provided free access to water, PKC-alpha -/- mice showed approximately 50% greater urine flow rate and lower urinary osmolality in 24-h metabolic cage experiments despite a greater urinary vasopressin-to-creatinine ratio vs. PKC-alpha +/+ mice. Renal albumin excretion was not different. Clearance experiments under inactin/ketamine anesthesia revealed a modestly reduced glomerular filtration rate and showed a reduced absolute and fractional renal fluid reabsorption in PKC-alpha -/- mice. The sodium-restricting response to a low-sodium diet was unaffected in PKC-alpha -/- mice. Urinary osmolality was reduced to similar hypotonic levels in PKC-alpha -/- and +/+ mice during acute oral water loading or application of the vasopressin V(2)-receptor antagonist SR-121463. In comparison, the lower urinary osmolality observed in PKC-alpha -/- mice vs. wild-type mice under basal conditions persisted during water restriction for 36 h. In conclusion, PKC-alpha appears not to play a major role in renal sodium reabsorption but, consistent with its expression in the medullary collecting duct, contributes to urinary concentration in mice. Considering that PKC-beta I and -beta II are coexpressed with PKC-alpha in mouse medullary collecting duct, the present results indicate that conventional PKC isoenzymes cannot fully compensate for each other.
在小鼠肾脏中，传统蛋白激酶C（PKC）同工酶α在肾小球、皮质集合管（仅闰细胞）和髓质集合管中表达。为深入了解其功能，对PKC-α基因敲除（-/-）和野生型（+/+）小鼠进行了研究。在24小时代谢笼实验中，当给予自由饮水时，尽管PKC-α -/-小鼠的尿血管加压素与肌酐比值高于PKC-α +/+小鼠，但前者的尿流率高出约50%，尿渗透压较低。肾白蛋白排泄无差异。在戊巴比妥钠/氯胺酮麻醉下进行的清除实验显示，PKC-α -/-小鼠的肾小球滤过率略有降低，绝对和分数肾液体重吸收减少。PKC-α -/-小鼠对低钠饮食的限钠反应未受影响。在急性口服水负荷或应用血管加压素V(2)受体拮抗剂SR-121463期间，PKC-α -/-和+/+小鼠的尿渗透压均降至相似的低渗水平。相比之下，在基础条件下观察到的PKC-α -/-小鼠与野生型小鼠相比较低的尿渗透压在限水36小时期间持续存在。总之，PKC-α似乎在肾钠重吸收中不发挥主要作用，但与其在髓质集合管中的表达一致，对小鼠的尿液浓缩有贡献。鉴于PKC-β I和-β II在小鼠髓质集合管中与PKC-α共表达，目前的结果表明传统PKC同工酶不能完全相互补偿。
