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Decreased aquaporin-2 expression and apical plasma membrane delivery in kidney collecting ducts of polyuric hypercalcemic rats.
- Source :
-
Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 1998 Dec; Vol. 9 (12), pp. 2181-93. - Publication Year :
- 1998
-
Abstract
- Hypercalcemia is frequently associated with a urinary concentrating defect and overt polyuria. The molecular mechanisms underlying this defect are poorly understood. Dysregulation of aquaporin-2 (AQP2), the predominant vasopressin-regulated water channel, is known to be associated with a range of congenital and acquired water balance disorders including nephrogenic diabetes insipidus and states of water retention. This study examines the effect of hypercalcemia on the expression of AQP2 in rat kidney. Rats were treated orally for 7 d with dihydrotachysterol, which produced significant hypercalcemia with a 15 +/- 2% increase in plasma calcium concentration. Immunoblotting and densitometry of membrane fractions revealed a significant decrease in AQP2 expression in kidney inner medulla of hypercalcemic rats to 45.7 +/- 6.8% (n = 11) of control levels (100 +/- 12%, n = 9). A similar reduction in AQP2 expression was seen in cortex (36.9 +/- 4.2% of control levels, n = 6). Urine production increased in parallel, from 11.3 +/- 1.4 to a maximum of 25.3 +/- 1.9 ml/d (P < 0.01), whereas urine osmolality decreased from 2007 +/- 186 mosmol/kg x H2O to 925 +/- 103 mosmol/kg x H2O (P < 0.01). Immunocytochemistry confirmed a decrease in total AQP2 labeling of collecting duct principal cells from kidneys of hypercalcemic rats, and reduced apical labeling. Immunoelectron microscopy demonstrated a significant reduction in AQP2 labeling of the apical plasma membrane, consistent with the development of polyuria. In summary, the results strongly suggest that AQP2 downregulation and reduced apical plasma membrane delivery of AQP2 play important roles in the development of polyuria in association with hypercalcemia.
- Subjects :
- Animals
Aquaporin 2
Aquaporin 6
Aquaporins biosynthesis
Aquaporins genetics
Body Water metabolism
Cell Polarity
Dihydrotachysterol toxicity
Diuresis
Hypercalcemia chemically induced
Hypercalcemia physiopathology
Immunoenzyme Techniques
Kidney Cortex metabolism
Kidney Medulla metabolism
Kidney Tubules, Collecting physiopathology
Male
Microscopy, Immunoelectron
Osmolar Concentration
Polyuria metabolism
Polyuria physiopathology
RNA, Messenger analysis
Rats
Rats, Wistar
Subcellular Fractions metabolism
Urine chemistry
Aquaporins deficiency
Hypercalcemia metabolism
Kidney Tubules, Collecting metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1046-6673
- Volume :
- 9
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of the American Society of Nephrology : JASN
- Publication Type :
- Academic Journal
- Accession number :
- 9848772
- Full Text :
- https://doi.org/10.1681/ASN.V9122181