Pathways of urea transport in the mammalian kidney

Knepper, Mark A.; Roch-Ramel, F

doi:10.1038/ki.1987.44

Cited by 92 publications

(51 citation statements)

References 30 publications

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“…Increase in basolateral solution osmolality by addition of raffinose (100 mosmol/kg H20) caused an 3. This estimate was made as described,2 except that Pf and ours were varied systematically using a two-dimensional parameter search (subroutine DUMINF; IMSL, Houston, TX) to find the values that minimized the sum of squared deviations (simulated minus experimental) of cell volume at all experimental data points.…”

Section: Resultsmentioning

confidence: 99%

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Apical membrane limits urea permeation across the rat inner medullary collecting duct.

Star¹

1990

J. Clin. Invest.

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Urea diffuses across the terminal inner medullary collecting duct (IMCD) via a facilitated transport pathway. To examine the mechanism of transcellular urea transport, membrane-apparent urea (Pme) and osmotic water (Pf) permeabilities of IMCD cells were measured by quantitative light microscopy in isolated IMCD-2 tubules perfused in the absence of vasopressin. Basolateral membrane Pf, determined by addition of raffinose to the bath, was 69 ,um/s. Basolateral membrane Pri, determined by substituting urea for raffinose without change in osmolality, was 14 X iO-5 cm/s. Bath phloretin inhibited basolateral P.,,m, by 85% without a significant effect on Pf. The basolateral reflection coefficient for urea, determined by addition of urea in the presence of phloretin, was 1.0. These results indicate that urea crosses the basolateral membrane by diffusion, and not by solvent drag. In perfused tubules, the rate of cell swelling following substitution of urea for mannitol was significantly greater with bath than lumen changes. After correcting for membrane surface area, the basolateral membrane was twofold more permeable than the apical membrane. Conclusions: (a) in the absence of vasopressin, urea permeation across the IMCD cell is limited by the apical membrane; (b) the basolateral membrane contains a phloretin-sensitive urea transporter, (c) transepithelial urea transport occurs by movement of urea through the IMCD cell. (J. Clin. Invest. 1990.

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Section: Resultsmentioning

confidence: 99%

“…Accumulation of urea in the inner medullary interstitium occurs by passive diffusion of urea from the terminal IMCD (3,4). The measured apical and basolateral membrane urea permeabilities are sufficiently large so that urea transport across the terminal IMCD occurs by a transcellular route.…”

Section: Discussionmentioning

confidence: 99%

Apical membrane limits urea permeation across the rat inner medullary collecting duct.

Star¹

1990

J. Clin. Invest.

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“…When perfused, these tubules had a morphologic appearance consistent with that previously observed in the urea-permeable part of the inner medullary collecting duct (terminal IMCD) (6). The tubule dissections were carried out at 15C in solution 1, 3, or 5 (Table I) chosen to match the initial perfusate solution. The dissected tubules were mounted on concentric pipets for in vitro microperfusion at 370C using method of Burg (14).…”

Section: Methodsmentioning

confidence: 99%

“…Thus, the action of vasopressin to increase urea permeability appears to be uniquely associated with the terminal IMCD. Urea reabsorption from the terminal collecting duct supplies most of the urea that accumulates in the inner medulla (5,6). Consequently, urea transport across the pressin are important components of the urinary concentrating mechanism.…”

Section: Introductionmentioning

confidence: 99%

Calcium and cyclic adenosine monophosphate as second messengers for vasopressin in the rat inner medullary collecting duct.

Star¹,

Nonoguchi²,

Balaban³

et al. 1988

J. Clin. Invest.

217

137

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Vasopressin increases both the urea permeability and osmotic water permeability in the terminal part of the renal inner medullary collecting duct (terminal IMCD). To identify the second messengers that mediate these responses, we measured urea permeability, osmotic water permeability, intracellular calcium concentration, and cyclic AMP accumulation in isolated terminal IMCDs. After addition of vasopressin, a transient rise in intracellular calcium occurred that was coincident with increases in cyclic AMP accumulation and urea permeability. Half-maximal increases in urea permeability and osmotic water permeability occurred with 0.01 nM vasopressin. The threshold concentration for a measurable increase in cyclic AMP accumulation was -0.01 nM, while measurable increases in intracellular calcium required much higher vasopressin concentrations (> 0.1 nM). Exogenous cyclic AMP (1 mM 8-Br-cAMP) mimicked the effect of vasopressin on urea permeability but did not produce a measurable change in intracellular calcium concentration. Conclusions: (a) Cyclic AMP is the second messenger that mediates the urea permeability response to vasopressin in the rat terminal IMCD. (b) Vasopressin increases the intracellular calcium concentration in the rat terminal IMCD, but the physiological role of this response is not yet known.

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“…In addition to countercurrent exchange, urea recycling is believed to provide an important means of maintaining a high level of urea in the renal inner medulla (54). Recycling occurs when urea that is reabsorbed from the IMCD is re-secreted into the loop of Henle, causing it to be returned to the collecting duct lumen with the flow of tubule fluid (Figure 1).…”

Section: Urea Recyclingmentioning

confidence: 99%

Urea and Renal Function in the 21st Century

Fenton¹,

Knepper²

2007

Journal of the American Society of Nephrology

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115

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Since the turn of the 21st century, gene knockout mice have been created for all major urea transporters that are expressed in the kidney: the collecting duct urea transporters UT-A1 and UT-A3, the descending thin limb isoform UT-A2, and the descending vasa recta isoform UT-B. This article discusses the new insights that the results from studies in these mice have produced in the understanding of the role of urea in the urinary concentrating mechanism and kidney function. Following is a summary of the major findings: (1) Urea accumulation in the inner medullary interstitium depends on rapid transport of urea from the inner medullary collecting duct (IMCD) lumen via UT-A1 and/or UT-A3; (2) as proposed by Robert Berliner and colleagues in the 1950s, the role of IMCD urea transporters in water conservation is to prevent a urea-induced osmotic diuresis; (3) the absence of IMCD urea transport does not prevent the concentration of NaCl in the inner medulla, contrary to what would be predicted from the passive countercurrent multiplier mechanism in the form proposed by Kokko and Rector and Stephenson; (4) deletion of UT-B (vasa recta isoform) has a much greater effect on urinary concentration than deletion of UT-A2 (descending limb isoform), suggesting that the recycling of urea between the vasa recta and the renal tubules quantitatively is less important than classic countercurrent exchange; and (5) urea reabsorption from the IMCD and the process of urea recycling are not important elements of the mechanism of protein-induced increases in GFR. In addition, the clinical relevance of these studies is discussed, and it is suggested that inhibitors that specifically target collecting duct urea transporters have the potential for clinical use as potassium-sparing diuretics that function by creation of urea-dependent osmotic diuresis.

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Pathways of urea transport in the mammalian kidney

Cited by 92 publications

References 30 publications

Apical membrane limits urea permeation across the rat inner medullary collecting duct.

Apical membrane limits urea permeation across the rat inner medullary collecting duct.

Calcium and cyclic adenosine monophosphate as second messengers for vasopressin in the rat inner medullary collecting duct.

Urea and Renal Function in the 21st Century

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