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Forschungsdatenbank PMU-SQQUID

Thiazide-sensitive NaCl-cotransporter in the intestine: possible role of hydrochlorothiazide in the intestinal Ca2+ uptake.
Bazzini, C; Vezzoli, V; Sironi, C; Dossena, S; Ravasio, A; De Biasi, S; Garavaglia, M; Rodighiero, S; Meyer, G; Fascio, U; Fürst, J; Ritter, M; Bottà, G; Paulmichl, M;
J Biol Chem. 2005; 280(20): 19902-19910.
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Dossena Silvia
Paulmichl Markus
Ritter Markus

Abstract

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 Ca(2+) 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.


Useful keywords (using NLM MeSH Indexing)

Animals

Base Sequence

Calcium/metabolism

DNA, Complementary/genetics

HT29 Cells

Homeostasis

Humans

Hydrochlorothiazide/pharmacology*

Intestines/drug effects*

Intestines/metabolism*

Ion Transport/drug effects

Male

RNA, Messenger/genetics

RNA, Messenger/metabolism

Rats

Rats, Wistar

Receptors, Drug/genetics

Receptors, Drug/metabolism*

Reverse Transcriptase Polymerase Chain Reaction

Sodium Chloride Symporters

Symporters/genetics

Symporters/metabolism*