| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung and Blood Institutes, National Institutes of Health, Bethesda, MD, USA
2 Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung and Blood Institutes, National Institutes of Health, Bethesda, MD, USA; Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom
* To whom correspondence should be addressed. E-mail: ROFE{at}ana.au.dk.
The Gamble phenomenon (initially described over 70 years ago as; "an economy of water in renal function referable to urea") suggested that urea plays a special role in the urinary concentrating mechanism, and that the concentrating mechanism depends in some complex way on an interaction between NaCl and urea. In this study, the role of collecting duct urea transporters in the Gamble phenomenon was investigated in wild-type mice and mice in which the inner medulla collecting duct (IMCD) facilitative urea transporters, UT-A1 and UT-A3, had been deleted (UT-A1/3-/- mice). The general features of the Gamble phenomenon were confirmed in wild-type mice, namely: 1) the water requirement for the excretion of urea is less than for the excretion of an osmotically equivalent amount of NaCl; and 2) when fed various mixtures of urea and salt in the diet, less water is required for the excretion of the two substances together than the amount of water needed for the excretion of the two substances separately. In UT-A1/3-/- mice both of these elements of the phenomenon were absent, indicating that IMCD urea transporters play a central role in the Gamble phenomenon. A titration study in which wild-type mice were given progressively increasing amounts of urea showed that the ability of the kidney to reabsorb urea was saturable, resulting in osmotic diuresis above excretion rates of ~6000 µosmol/day. In the same titration experiments, when increasing amounts of NaCl were added to the diet, mice were unable to increase urinary NaCl concentrations to >420 mM, resulting in osmotic diuresis at NaCl excretion rates of ~3500 µosmol/day. Thus, both urea and NaCl can induce osmotic diuresis when large amounts are given, supporting the conclusion that the decrease in water excretion with mixtures of urea and NaCl added to the diet (compared to pure NaCl or urea) is due to the separate abilities of urea and NaCl to induce osmotic diuresis, rather than to any specific interaction of urea transport and NaCl transport at an epithelial level.
This article has been cited by other articles:
|
|
 |
|
  Y. Wang, J. D. Klein, M. A. Blount, C. F. Martin, K. J. Kent, V. Pech, S. M. Wall, and J. M. Sands Epac Regulates UT-A1 to Increase Urea Transport in Inner Medullary Collecting Ducts J. Am. Soc. Nephrol., September 1, 2009; 20(9): 2018 - 2024. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Hartman Bakken, L. G. Herrera M., R. M. Carroll, J. Ayala-Berdon, J. E. Schondube, and C. Martinez del Rio A nectar-feeding mammal avoids body fluid disturbances by varying renal function Am J Physiol Renal Physiol, December 1, 2008; 295(6): F1855 - F1863. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. L. Pannabecker, W. H. Dantzler, H. E. Layton, and A. T. Layton Role of three-dimensional architecture in the urine concentrating mechanism of the rat renal inner medulla Am J Physiol Renal Physiol, November 1, 2008; 295(5): F1271 - F1285. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Fenton and M. A. Knepper Urea and Renal Function in the 21st Century: Insights from Knockout Mice J. Am. Soc. Nephrol., March 1, 2007; 18(3): 679 - 688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Sands Critical Role of Urea in the Urine-Concentrating Mechanism J. Am. Soc. Nephrol., March 1, 2007; 18(3): 670 - 671. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
