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

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.

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