Loss of the anion exchanger DRA (Slc26a3), or PAT1 (Slc26a6), alters sulfate transport by the distal ileum and overall sulfate homeostasis

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 35SO42– and 36Cl– 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 (JmsSO4), 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 JmsSO4 and a 30% reduction to the secretory serosal-to-mucosal flux (JsmSO4). We propose that DRA, together with PAT1, contributes to JsmSO4 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 (USO4) 2.2-fold higher, in DRA-KO mice compared with WT controls, whereas USO4 was increased 1.8-fold in PAT1-KO mice. These alterations to sulfate homeos...
Source: AJP: Gastrointestinal and Liver Physiology - Category: Gastroenterology Authors: Tags: RESEARCH ARTICLE Source Type: research