HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 553/2/511    most recent jphysiol.2003.053363v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Amlal, H. Articles by Soleimani, M. Search for Related Content PubMed PubMed Citation Articles by Amlal, H. Articles by Soleimani, M.

Downregulation of renal AQP2 water channel and NKCC2 in mice lacking the apical Na⁺-H⁺ exchanger NHE3

Hassane Amlal*, Clara Ledoussal†, Sulaiman Sheriff‡, Gary E. Shull† and Manoocher Soleimani*§

The apical Na⁺-H⁺ exchanger NHE3 plays an important role in fluid reabsorption in the proximal tubule. However, whether its deletion alters the salt and water transport in the distal nephron remains unknown. To answer these questions, wild-type (Nhe3^+/+) and NHE3 null mice (Nhe3^-/-) were placed in metabolic cages and their water balance and urine osmolality were examined. Nhe3^-/- mice demonstrated a significant polydipsia (P < 0.03) and polyuria (P < 0.04), with a lower urine osmolality (P < 0.003) as compared to Nhe3^+/+ mice. Northern hybridization and immunoblotting studies indicated that the mRNA expression and protein abundance of the collecting duct (CD) water channel AQP2 decreased by 52 % (P < 0.0003) and 73 % (P < 0.003) in the cortex, and by 53 % and 54 % (P < 0.002) in the inner medulla (IM) of Nhe3^-/- vs. Nhe3^+/+ mice. The expression of AQP2 in the outer medulla (OM) remained unchanged. Further, the mRNA expression and protein abundance of the medullary thick ascending limb (mTAL) apical Na⁺-K⁺-2Cl^- cotransporter (NKCC2) decreased by 52 % (P < 0.02) and 44 % (P < 0.01), respectively, in the OM of Nhe3^-/- vs. Nhe3^+/+ mice. The circulating plasma levels of vasopressin as well as the mRNA expression of vasopressin prohormone were significantly increased in Nhe3^-/- vs. Nhe3^+/+ mice (P < 0.05). Studies in mice treated with acetazolamide indicated that increased bicarbonate and fluid delivery to distal nephron did not alter the expression of NKCC2 in mTAL and decreased AQP2 protein only in OM but not in the cortex or IM. In conclusion, mice lacking the apical NHE3 have impairment in their water balance and urine osmolality, which correlates with the downregulation of AQP2 expression. These defects occur despite increased circulating levels of vasopressin. We propose that an ADH-independent mechanism is responsible for the downregulation of AQP2 and the resulting polyuria in NHE3 null mice.

This article has been cited by other articles:

				R. A. Fenton and M. A. Knepper Mouse Models and the Urinary Concentrating Mechanism in the New Millennium Physiol Rev, October 1, 2007; 87(4): 1083 - 1112. [Abstract] [Full Text] [PDF]

				S. Petrovic, H. Amlal, X. Sun, F. Karet, S. Barone, and M. Soleimani Vasopressin induces expression of the Cl-/HCO3- exchanger SLC26A7 in kidney medullary collecting ducts of Brattleboro rats Am J Physiol Renal Physiol, May 1, 2006; 290(5): F1194 - F1201. [Abstract] [Full Text] [PDF]