title: Thiazide-sensitive NaCl-cotransporter in the intestine: possible role of hydrochlorothiazide in the intestinal Ca2+ uptake.
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.
authors.affiliation: Department of Biomolecular Sciences and Biotechnology, Università degli Studi di Milano, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bazzini
authors.forename: Valeria
authors.initials: V
authors.lastname: Vezzoli
authors.forename: Chiara
authors.initials: C
authors.lastname: Sironi
authors.forename: Silvia
authors.initials: S
authors.lastname: Dossena
authors.forename: Andrea
authors.initials: A
authors.lastname: Ravasio
authors.forename: Silvia
authors.initials: S
authors.lastname: De Biasi
authors.forename: Marialisa
authors.initials: M
authors.lastname: Garavaglia
authors.forename: Simona
authors.initials: S
authors.lastname: Rodighiero
authors.forename: Giuliano
authors.initials: G
authors.lastname: Meyer
authors.forename: Umberto
authors.initials: U
authors.lastname: Fascio
authors.forename: Johannes
authors.initials: J
authors.lastname: Fürst
authors.forename: Markus
authors.initials: M
authors.lastname: Ritter
authors.forename: Guido
authors.initials: G
authors.lastname: Bottà
authors.forename: Markus
authors.initials: M
authors.lastname: Paulmichl
mesh_terms: D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D019073:HT29 Cells; D006706:Homeostasis; D006801:Humans; D006852:Hydrochlorothiazide / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects*; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D049992:Sodium Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters / Q000235:genetics / Q000378:metabolism*
chemical_list: D018076:DNA, Complementary; D012333:RNA, Messenger; D011955:Receptors, Drug; C578874:SLC12A3 protein, human; C578876:Slc12a3 protein, rat; D049992:Sodium Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; C064415:thiazide receptor; D006852:Hydrochlorothiazide; D002118:Calcium