Evidence for a role of protein kinase C- in urine concentration

Abstract

Yao, Lijun, Dan-Yang Huang, Imke L. Pfaff, Xin Nie, Michael Leitges, and Volker Vallon. Evidence for a role of protein kinase Cin urine concentration. Am J Physiol Renal Physiol 287: F299– F304, 2004. First published March 23, 2004; 10.1152/ajprenal. 00274.2003.—In mouse kidney, the conventional protein kinase C (PKC) isoenzyme is expressed in glomeruli, the cortical collecting duct (intercalated cells only), and medullary collecting duct. To get insights on its function, PKCknockout ( / ) and wild-type ( / ) mice were studied. When provided free access to water, PKC/ mice showed 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/ 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/ mice. The sodium-restricting response to a low-sodium diet was unaffected in PKC/ mice. Urinary osmolality was reduced to similar hypotonic levels in PKC/ and / mice during acute oral water loading or application of the vasopressin V2-receptor antagonist SR-121463. In comparison, the lower urinary osmolality observed in PKC/ mice vs. wild-type mice under basal conditions persisted during water restriction for 36 h. In conclusion, PKCappears 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 PKCI and II are coexpressed with PKCin mouse medullary collecting duct, the present results indicate that conventional PKC isoenzymes cannot fully compensate for each other.