Urinary concentrating defect in mice with selective deletion of phloretin-sensitive urea transporters in the renal collecting duct
TLDR
Analysis of inner medullary tissue after water restriction revealed marked depletion of urea in UT-A1/3(-/-) mice, confirming the concept that phloretin-sensitive IMCD urea transporters play a central role in Medullary urea accumulation.Abstract:
To investigate the role of inner medullary collecting duct (IMCD) urea transporters in the renal concentrating mechanism, we deleted 3 kb of the UT-A urea transporter gene containing a single 140-bp exon (exon 10). Deletion of this segment selectively disrupted expression of the two known IMCD isoforms of UT-A, namely UT-A1 and UT-A3, producing UT-A1/3-/- mice. In isolated perfused IMCDs from UT-A1/3-/- mice, there was a complete absence of phloretin-sensitive or vasopressin-stimulated urea transport. On a normal protein intake (20% protein diet), UT-A1/3-/- mice had significantly greater fluid consumption and urine flow and a reduced maximal urinary osmolality relative to wild-type controls. These differences in urinary concentrating capacity were nearly eliminated when urea excretion was decreased by dietary protein restriction (4% by weight), consistent with the 1958 Berliner hypothesis stating that the chief role of IMCD urea transport in the concentrating mechanism is the prevention of urea-induced osmotic diuresis. Analysis of inner medullary tissue after water restriction revealed marked depletion of urea in UT-A1/3-/- mice, confirming the concept that phloretin-sensitive IMCD urea transporters play a central role in medullary urea accumulation. However, there were no significant differences in mean inner medullary Na+ or Cl- concentrations between UT-A1/3-/- mice and wild-type controls, indicating that the processes that concentrate NaCl were intact. Thus, these results do not corroborate the predictions of passive medullary concentrating models stating that NaCl accumulation in the inner medulla depends on rapid vasopressin-regulated urea transport across the IMCD epithelium.read more
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References
More filters
Journal ArticleDOI
Function of the thick ascending limb of Henle's loop.
Maurice B. Burg,Nordica Green +1 more
TL;DR: Water permeability (Lp) is low, which combined with the NaCl transport accounts for the dilution of the urine in this segment, and Na permeability is greater than Cl permeability, as indicated by radioisotope measurements of ion fluxes.
Journal ArticleDOI
Sodium chloride and water transport in the medullary thick ascending limb of Henle. Evidence for active chloride transport.
Antonino S. Rocha,Juha P. Kokko +1 more
TL;DR: The medullary thick ascending limb of Henle is water impermeable while having the capacity for active outward solute transport as a consequence of an electrogenic chloride pump and the combination of these characteristics allows this segment to generate a dilute tubular fluid and participate as the principal energy source for the overall operation of the countercurrent multiplication system.
Journal ArticleDOI
Countercurrent multiplication system without active transport in inner medulla
Juha P. Kokko,Floyd C. Rector +1 more
TL;DR: This model is based largely on transport characteristics obtained by perfusing isolated segments of rabbit nephrons in vitro, and allows the entire system to operate by passive diffusion of NaCl out of the thin ALH.
Journal ArticleDOI
Dilution and concentration of the urine and the action of antidiuretic hormone.
Journal ArticleDOI
Long-term regulation of four renal aquaporins in rats
TL;DR: It is concluded that changes in interstitial osmolality are not necessary for the AVP-induced upregulation of aquaporin-2 and aquaporIn-3 expression, which is increased in response to elevated circulating AVP.