Thiazide-sensitive NaCl-cotransporter in the intestine: possible role of hydrochlorothiazide in the intestinal Ca2+ uptake.
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.
Bazzini
Claudia
C
Department of Biomolecular Sciences and Biotechnology, Università degli Studi di Milano, Italy.
Vezzoli
Valeria
V
Sironi
Chiara
C
Dossena
Silvia
S
Ravasio
Andrea
A
De Biasi
Silvia
S
Garavaglia
Marialisa
M
Rodighiero
Simona
S
Meyer
Giuliano
G
Fascio
Umberto
U
Fürst
Johannes
J
Ritter
Markus
M
Bottà
Guido
G
Paulmichl
Markus
M
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*
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