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.
Yao
Lijun
L
Institute of Pharmacology and Toxicology, University of Tübingen, 72074 Tuebingen, Germany.
Huang
Dan-Yang
DY
Pfaff
Imke L
IL
Nie
Xin
X
Leitges
Michael
M
Vallon
Volker
V
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D051399:Aquaporin 2; D020346:Aquaporins / Q000378:metabolism; D015194:Diffusion Chambers, Culture; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000033:anatomy & histology / Q000502:physiology; D007671:Kidney Concentrating Ability / Q000502:physiology*; D007679:Kidney Medulla / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009025:Morpholines / Q000494:pharmacology; D009318:Natriuresis; D009929:Organ Size; D011493:Protein Kinase C / Q000502:physiology*; D051571:Protein Kinase C-alpha; D012964:Sodium / Q000172:deficiency; D012982:Sodium, Dietary / Q000008:administration & dosage; D013141:Spiro Compounds / Q000494:pharmacology; D014867:Water / Q000494:pharmacology; D014868:Water Deprivation / Q000502:physiology
D065092:Antidiuretic Hormone Receptor Antagonists; C496024:Aqp2 protein, mouse; D051399:Aquaporin 2; D020346:Aquaporins; D009025:Morpholines; D012982:Sodium, Dietary; D013141:Spiro Compounds; D014867:Water; D012964:Sodium; C103281:satavaptan; C496630:Prkca protein, mouse; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha