Dynamic Regulation of CFTR Bicarbonate Permeability by [Cl−]i and Its Role in Pancreatic Bicarbonate Secretion

Park, Hyun Woo; Nam, Joo Hyun; Kim, Joo Young; Namkung, W.; Yoon, Jae Seok; Lee, Jung–Soo; Kim, Kyung Sik; Venglovecz, Viktória; Gray, Michael A.; Kim, Kyung Hwan; Lee, Min Goo

doi:10.1053/j.gastro.2010.04.004

Cited by 173 publications

(211 citation statements)

References 30 publications

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“…7C) were enhanced at acidic extracellular pH, consistent with H ϩ /anion cotransport or with anion/OH Ϫ exchange. Either mechanism is supported by the observed stimulation of 35 SO 4 2Ϫ efflux upon elevating pH o from 5.0 to 7.4 (Fig. 7E).…”

Section: C293supporting

confidence: 59%

“…Na 36 Cl was from GE Healthcare (Pittsburgh, PA), Na2 35 SO 4 2Ϫ was from PerkinElmer (Waltham, MA), and [ 14 C]oxalate was from NEN-DuPont (now PerkinElmer). Restriction enzymes were from New England Biolabs (Beverly, MA).…”

Section: Methodsmentioning

confidence: 99%

“…For 35 SO 4 2Ϫ efflux assay, oocytes were injected with 50 nl of ϳ1 mCi Na2 35 SO 4 2Ϫ (ϳ30,000 cpms) with estimated final intracellular [SO 4 2Ϫ ] concentration of 1 or 14 mM. SO 4 2Ϫ efflux experiments were carried out in ND-96 or in baths containing 20 mM Na2SO4 plus 66 mM Na isethionate (6).…”

Section: Methodsmentioning

confidence: 99%

“…Ovarian segments were excised from adult female 35 SO 4 2Ϫ in the presence of 1 or 20 mM unlabeled sulfate. All influx assays were conducted over 30-min periods.…”

Section: Methodsmentioning

confidence: 99%

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SLC26 anion exchangers of guinea pig pancreatic duct: molecular cloning and functional characterization

Stewart

Shmukler

Vandorpe

et al. 2011

American Journal of Physiology-Cell Physiology

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The secretin-stimulated human pancreatic duct secretes HCO3−-rich fluid essential for normal digestion. Optimal stimulation of pancreatic HCO3− secretion likely requires coupled activities of the cystic fibrosis transmembrane regulator (CFTR) anion channel and apical SLC26 Cl−/HCO3− exchangers. However, whereas stimulated human and guinea pig pancreatic ducts secrete ∼140 mM HCO3− or more, mouse and rat ducts secrete ∼40–70 mM HCO3−. Moreover, the axial distribution and physiological roles of SLC26 anion exchangers in pancreatic duct secretory processes remain controversial and may vary among mammalian species. Thus the property of high HCO3− secretion shared by human and guinea pig pancreatic ducts prompted us to clone from guinea pig pancreatic duct cDNAs encoding Slc26a3, Slc26a6, and Slc26a11 polypeptides. We then functionally characterized these anion transporters in Xenopus oocytes and human embryonic kidney (HEK) 293 cells. In Xenopus oocytes, gpSlc26a3 mediated only Cl−/Cl− exchange and electroneutral Cl−/HCO3− exchange. gpSlc26a6 in Xenopus oocytes mediated Cl−/Cl− exchange and bidirectional exchange of Cl− for oxalate and sulfate, but Cl−/HCO3− exchange was detected only in HEK 293 cells. gpSlc26a11 in Xenopus oocytes exhibited pH-dependent Cl−, oxalate, and sulfate transport but no detectable Cl−/HCO3− exchange. The three gpSlc26 anion transporters exhibited distinct pharmacological profiles of 36Cl− influx, including partial sensitivity to CFTR inhibitors Inh-172 and GlyH101, but only Slc26a11 was inhibited by PPQ-102. This first molecular and functional assessment of recombinant SLC26 anion transporters from guinea pig pancreatic duct enhances our understanding of pancreatic HCO3− secretion in species that share a high HCO3− secretory output.

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Section: C293supporting

confidence: 59%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Ovarian segments were excised from adult female 35 SO 4 2Ϫ in the presence of 1 or 20 mM unlabeled sulfate. All influx assays were conducted over 30-min periods.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

SLC26 anion exchangers of guinea pig pancreatic duct: molecular cloning and functional characterization

Stewart

Shmukler

Vandorpe

et al. 2011

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

show abstract

“…The conserved wide distribution of CFTR and sAC in various cell types suggests that the presently demonstrated CFTR-HCO 3 − -dependent signaling pathway may have implications in other cellular processes far beyond embryo development. Of interest, CFTR expression and its channel activity are also found to be regulated by various environmental factors, such as hypoxia [57], ion concentrations [58,59] and mechanical stimulation [60], suggesting its potential in sensing a wide spectrum of environmental changes and converting these changes into epigenetic changes, such as miRNA alteration, in the cell under various physiological and pathological conditions.…”

Section: Discussionmentioning

confidence: 99%