期刊
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
卷 313, 期 3, 页码 G166-G179出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00079.2017
关键词
Ussing chamber; chloride secretion; Slc13a1; Slc26a1; downregulated in adenoma; putative anion transporter 1
资金
- National Institute of Diabetes and Digestive and Kidney Diseases [56245, 81624, 88892]
The ileum is considered the primary site of inorganic sulfate (SO42-) absorption. In the present study, we explored the contributions of the apical chloride/bicarbonate (Cl- /HCO3-) exchangers downregulated in adenoma (DRA; Slc26a3), and putative anion transporter 1 (PAT1; Slc26a6), to the underlying transport mechanism. Transepithelial (SO42-)-S-35 and Cl-36(-) fluxes were determined across isolated, short-circuited segments of the distal ileum from wild-type (WT), DRA-knockout (KO), and PAT1-KO mice, together with measurements of urine and plasma sulfate. The WT distal ileum supported net sulfate absorption [197.37 +/- 13.61 (SE) nmol.cm(-2).h(-1)], but neither DRA nor PAT1 directly contributed to the unidirectional mucosal-to-serosal flux (Jms SO4), which was sensitive to serosal (but not mucosal) DIDS, dependent on Cl-, and regulated by cAMP. However, the absence of DRA significantly enhanced net sulfate absorption by one-third via a simultaneous rise in J(ms)(SO4) and a 30% reduction to the secretory serosal-to-mucosal flux (J(sm)(SO4)). We propose that DRA, together with PAT1, contributes to J(sm)(SO4) by mediating sulfate efflux across the apical membrane. Associated with increased ileal sulfate absorption in vitro, plasma sulfate was 61% greater, and urinary sulfate excretion (U-SO4) 2.2-fold higher, in DRA-KO mice compared with WT controls, whereas U-SO4 was increased 1.8-fold in PAT1-KO mice. These alterations to sulfate homeostasis could not be accounted for by any changes to renal sulfate handling suggesting that the source of this additional sulfate was intestinal. In summary, we characterized transepithelial sulfate fluxes across the mouse distal ileum demonstrating that DRA (and to a lesser extent, PAT1) secretes sulfate with significant implications for intestinal sulfate absorption and overall homeostasis. NEW & NOTEWORTHY Sulfate is an essential anion that is actively absorbed from the small intestine involving members of the Slc26 gene family. Here, we show that the main intestinal chloride transporter Slc26a3, known as downregulated in adenoma (DRA), also handles sulfate and contributes to its secretion into the lumen. In the absence of functional DRA (as in the disease congenital chloride diarrhea), net intestinal sulfate absorption was significantly enhanced resulting in substantial alterations to overall sulfate homeostasis.
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