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

J. Biol. Chem., Vol. 280, Issue 20, 19902-19910, May 20, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/20/19902    most recent M411961200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bazzini, C. Articles by Paulmichl, M. Search for Related Content PubMed PubMed Citation Articles by Bazzini, C. Articles by Paulmichl, M. Social Bookmarking                      What's this?

Thiazide-sensitive NaCl-cotransporter in the Intestine

POSSIBLE ROLE OF HYDROCHLOROTHIAZIDE IN THE INTESTINAL Ca²⁺ UPTAKE^*

Claudia Bazzini, Valeria Vezzoli, Chiara Sironi, Silvia Dossena, Andrea Ravasio, Silvia De Biasi, MariaLisa Garavaglia, Simona Rodighiero¶, Giuliano Meyer, Umberto Fascio¶, Johannes Fürst, Markus Ritter||, Guido Bottà**, and Markus Paulmichl¶

From the Department of Biomolecular Sciences and Biotechnology, Università degli Studi di Milano, Via Celoria 26, I-20133 Milan, Italy, the Department of Physiology and Medical Physics, Innsbruck Medical University, Fritz-Pregl Strasse 3, A-6020 Innsbruck, Austria, the ^¶Centro Interdipartimentale di Microscopia Aranzata and Centro Interdisciplinare Materiali e Interfacce Nanostruturali, Via Celoria 26, I-20133 Milan, Italy, and the ^||Paracelsus Private Medical University, Strubergasse 21, A-5020 Salzburg, Austria

Thiazides, such as hydrochlorothiazide (HCTZ), are used to control blood pressure and to reduce renal calcium excretion. These effects are a result of interactions with the NaCl-cotransporter (NCC). This is demonstrated by the fact that mutations within the NCC protein lead to salt-resistant hypotension and hypocalciuria, paralleled by an increase in bone mineral density. These symptoms are also known as Gitelman syndrome. It has become increasingly evident that the effect of HCTZ on blood pressure and calcium homeostasis cannot be attributed exclusively to kidney functions, where the primary action of HCTZ on NCC is postulated to occur. We demonstrated the presence of the NCC transporter in the rat small intestine (ileum and jejunum) and human HT-29 cells, by using reverse transcription-PCR, Northern blot, Western blot, and immunofluorescence. Furthermore, we show that HCTZ modulates Ca²⁺ uptake by intestinal cells, while affecting the electrical parameters of the cellular membrane, thus suggesting a functional interaction between NCC and the epithelial voltage-dependent calcium channel. The experiments presented here support the hypothesis of a direct involvement of the intestinal cells in the interaction between HCTZ and NaCl, as well as calcium homeostasis.

Received for publication, October 21, 2004 , and in revised form, March 21, 2005.

^* This research was supported by the Italian Ministry of Instruction, University and Research (Fondo per gli Investimenti della Ricerca di Base (FIRB) RBAU01RANB_003). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^** To whom correspondence may be addressed. Tel.: 39-02-5031-4947; Fax: 39-02-5031-4948; E-mail: guido.botta{at}unimi.it. To whom correspondence may be addressed. Tel.: 43-512-507-3756; Fax: 43-512-577-656; E-mail: markus.paulmichl{at}uibk.ac or markus.paulmichl{at}unimi.it.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. L. Geller and J. S. Adams Statins and fracture: are all variables accounted for? Arch Intern Med, May 8, 2006; 166(9): 1041 - 1041. [Full Text] [PDF]

				J. A. Riancho, G. Saro, C. Sanudo, M. J. Izquierdo, and M. T. Zarrabeitia Gitelman syndrome: genetic and expression analysis of the thiazide-sensitive sodium-chloride transporter in blood cells Nephrol. Dial. Transplant., January 1, 2006; 21(1): 217 - 220. [Abstract] [Full Text] [PDF]