| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Lohi, H, et al.
(författare)
-
Isoforms of SLC26A6 mediate anion transport and have functional PDZ interaction domains
- 2003
-
Ingår i: American journal of physiology. Cell physiology. - : American Physiological Society. - 0363-6143 .- 1522-1563. ; 284:3, s. C769-C779
-
Tidskriftsartikel (refereegranskat)abstract
- The solute carrier gene family SLC26 consists of tissue-specific anion exchanger genes, three of them associated with distinct human recessive disorders. By a genome-driven approach, several new SLC26 family members have been identified, including a kidney- and pancreas-specific gene, SLC26A6. We report the functional characterization of SLC26A6 and two new alternatively spliced variants, named SLC26A6c and SLC26A6d. Immunofluorescence studies on transiently transfected cells indicated membrane localization and indicated that both NH2- and COOH-terminal tails of the SLC26A6 variants are located intracellularly, suggesting a topology with an even number of transmembrane domains. Functional expression of the three proteins in Xenopus oocytes demonstrated Cl−and SO[Formula: see text] transport activity. In addition, the transport of SO[Formula: see text] and Cl−was inhibited by DIDS and HCO[Formula: see text]. We demonstrated also that the COOH terminus of SLC26A6 binds to the first and second PDZ domains of the Na+/H+exchanger (NHE)3 kinase A regulatory protein (E3KARP) and NHE3 regulatory factor (NHERF) proteins in vitro. Truncation of the last three amino acids (TRL) of SLC26A6 abrogated the interaction but did not affect transport function. These results demonstrate that SLC26A6 and its two splice variants can function as anion transporters linked to PDZ-interaction pathways. Our results support the general concept of microdomain organization for ion transport and suggest a mechanism for cystic fibrosis transmembrane regulator (CFTR)-mediated SLC26A6 upregulation in pancreatic duct cells.
|
|
| 6. |
- Petrovic, S, et al.
(författare)
-
Identification of a basolateral Cl-/HCO3- exchanger specific to gastric parietal cells
- 2003
-
Ingår i: American journal of physiology. Gastrointestinal and liver physiology. - : American Physiological Society. - 0193-1857 .- 1522-1547. ; 284:6, s. G1093-G1103
-
Tidskriftsartikel (refereegranskat)abstract
- The basolateral Cl−/HCO[Formula: see text] exchanger in parietal cells plays an essential role in gastric acid secretion mediated via the apical gastric H+-K+-ATPase. Here, we report the identification of a new Cl−/HCO[Formula: see text]exchanger, which shows exclusive expression in mouse stomach and kidney, with expression in the stomach limited to the basolateral membrane of gastric parietal cells. Tissue distribution studies by RT-PCR and Northern hybridizations demonstrated the exclusive expression of this transporter, also known as SLC26A7, to stomach and kidney, with the stomach expression significantly more abundant. No expression was detected in the intestine. Cellular distribution studies by RT-PCR and Northern hybridizations demonstrated predominant localization of SLC26A7 in gastric parietal cells. Immunofluorescence labeling localized this exchanger exclusively to the basolateral membrane of gastric parietal cells, and functional studies in oocytes indicated that SLC26A7 is a DIDS-sensitive Cl−/HCO[Formula: see text] exchanger that is active in both acidic and alkaline pHi. On the basis of its unique expression pattern and function, we propose that SLC26A7 is a basolateral Cl−/HCO[Formula: see text] exchanger in gastric parietal cells and plays a major role in gastric acid secretion.
|
|
| 7. |
- Pihl, Liselotte, et al.
(författare)
-
Motility-induced but not vasoactive intestinal peptide-induced increase in luminal alkalinization in rat duodenum is dependent on luminal Cl-
- 2010
-
Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 200:2, s. 181-191
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: To investigate whether the motility- and the vasoactive intestinal peptide (VIP)-induced increase in luminal alkalinization in the duodenum is dependent on luminal Cl-. Methods: Experiments were performed in anaesthetized rats in vivo. The proximal duodenum was perfused luminally with an isotonic solution, containing zero or low Cl- and the effects on luminal alkalinization, motility, fluid flux and epithelial permeability were determined. Parecoxib, a COX-2 inhibitor, was used to induce duodenal contractions. Results: Control rats lacked duodenal wall contractions while parecoxib-treated ones exhibited contractions throughout the experiment. Most animals had a net fluid absorption during the perfusion with isotonic NaCl. Luminal alkalinization was about 100% higher in parecoxib-treated rats than in controls. Cl--free solutions did not affect epithelial permeability or motility but decreased luminal alkalinization by >= 50% and decreased net fluid absorption in both control and parecoxib-treated animals. Reduction in luminal Cl- decreased alkalinization in a concentration-dependent manner. The parecoxib-induced increase in alkalinization was markedly reduced in the absence of luminal Cl-. VIP increased luminal alkalinization and induced fluid secretion. The lack of luminal Cl- did not affect the VIP-induced increase in alkalinization but reduced fluid secretion. Conclusions: The parecoxib-induced increase in luminal alkalinization is highly dependent on luminal Cl- and it is proposed that COX-2 inhibition, via induction of duodenal motility, enhances HCO3- efflux through stimulation of apical Cl-/HCO3- exchange in duodenal epithelial cells. Although the VIP-induced stimulation of fluid secretion is partly dependent on luminal Cl-, the VIP-induced increase in luminal alkalinization is not.
|
|
| 8. |
- Singh, A K, et al.
(författare)
-
CFTR and its key role in in vivo resting and luminal acid-induced duodenal HCO3-secretion
- 2008
-
Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 193:4, s. 357-365
-
Tidskriftsartikel (refereegranskat)abstract
- Background and aims: We investigated the role of the recently discovered, villous-expressed anion exchanger Slc26a6 (PAT1) and the predominantly crypt-expressed cystic fibrosis transmembrane regulator (CFTR) in basal and acid-stimulated murine duodenal HCO3− secretion in vivo, and the influence of blood HCO3− concentration on both.Methods: The proximal duodenum of anaesthetized mice was perfused in situ, and HCO3− secretion was determined by back-titration. Duodenal mucosal permeability was assessed by determining 51Cr-EDTA leakage from blood to lumen.Results: Compared with wild type (WT) littermates basal duodenal HCO3− secretory rates were slightly reduced in Slc26-deficient mice at low (∼21 mm), and markedly reduced at high blood HCO3− concentration (∼29 mm). In contrast, basal HCO3− secretion was markedly reduced in CFTR-deficient mice compared with WT littermates both at high and low blood HCO3− concentration. A short-term application of luminal acid increased duodenal HCO3− secretory rate in Slc26a6-deficient and WT mice to the same degree, but had no stimulatory effect in the absence of CFTR. Luminal acidification to pH 2.5 did not alter duodenal permeability.Conclusions: The involvement of Slc26a6 in basal HCO3− secretion in murine duodenum in vivo is critically dependent on the systemic acid/base status, and this transporter is not involved in acid-stimulated HCO3− secretion. The presence of CFTR is essential for basal and acid-induced HCO3− secretion irrespective of acid/base status. This suggests a coupled action of Slc26a6 with CFTR for murine basal duodenal HCO3− secretion, but not acid-stimulated secretion, in vivo.
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
