Renal carbonic anhydrase activity in DBA/2FG-pcy/pcy mice with inherited polycystic kidney disease.
DBA/2FG-pcy/pcy (D2-pcy) mice are a hereditary murine model of slowly progressive polycystic kidney disease (PKD) and characterized by the persistent excretion of acidic urine, in association with polyuria, after weaning. In this study, the activity of carbonic anhydrase (CA) and it histological distribution in the kidney of D2-pcy mice were investigated by immunohistochemistry. Significantly higher CA activity was detected in the cytosolic, but not membrane, fraction of kidney homogenates in 5-week-old D2-pcy mice than in age-matched, control DBA/2 (D2) mice, and a more rapid rate of urine acidification was noted in 11-week-old mice when acetazolamide, an inhibitor of the enzyme, was administered orally. By immunohistochemistry for the major renal CA isoenzyme (CA II), epithelial cells in the distal straight tubules and the cortical collecting ducts were stained intensely, whereas those of the proximal convoluted tubules had only weak and diffuse staining. The glomeruli, the proximal straight tubules and the ascending thin limb of Henle's loop were almost free from staining. In the cells lining cysts and/or dilated tubules, CA II activity was well preserved, although the staining intensity was considerably reduced in fully-flattened, lining cells of cysts, but no difference was found between D2-pcy and D2 mice in any segmental localization of renal CA II activity. From these results it seems that D2-pcy mice in the early stages of the cystic disease continue to secrete excess protons through the CA-mediated reaction that is stimulated for regulation of acid-base balance in the distal portion of the nephron and the collecting duct in kidney. It also suggests that monitoring urine pH may be useful in predicting the effects of early interventions on the progression of slowly developing renal cysts.
Kaneta
S
S
Department of Pharmacotherapeutics, Hokkaido College of Pharmacy, Otaru, Japan.
Ishizuki
S
S
Kasahara
M
M
Nagao
S
S
Takahashi
H
H
D000086:Acetazolamide / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002256:Carbonic Anhydrases / Q000378:metabolism*; D002458:Cell Fractionation; D004195:Disease Models, Animal; D006863:Hydrogen-Ion Concentration; D007124:Immunoenzyme Techniques; D007668:Kidney / Q000201:enzymology*; D007678:Kidney Glomerulus / Q000201:enzymology; D007684:Kidney Tubules / Q000201:enzymology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains / Q000235:genetics; D007690:Polycystic Kidney Diseases / Q000201:enzymology* / Q000235:genetics; D014554:Urination / Q000187:drug effects
D002256:Carbonic Anhydrases; D000086:Acetazolamide