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

Andrew K. Stewart; Boris E. Shmukler; David H. Vandorpe; Fabian Reimold; John F. Heneghan; M. Nakakuki; Arash Akhavein; Shigeru Ko; Hiroshi Ishiguro; Seth L. Alper

doi:10.1152/ajpcell.00089.2011

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

Andrew K. Stewart, Boris E. Shmukler, David H. Vandorpe, Fabian Reimold, John F. Heneghan, M. Nakakuki, Arash Akhavein, Shigeru Ko, Hiroshi Ishiguro, Seth L. Alper

Research output: Contribution to journal › Article › peer-review

42 Citations (Scopus)

Abstract

The secretin-stimulated human pancreatic duct secretes HCO ^- ₃ -rich fluid essential for normal digestion. Optimal stimulation of pancreatic HCO ^- ₃ secretion likely requires coupled activities of the cystic fibrosis transmembrane regulator (CFTR) anion channel and apical SLC26 Cl ^-/HCO ₃ ^- exchangers. However, whereas stimulated human and guinea pig pancreatic ducts secrete -140 mM HCO ₃ ^- or more, mouse and rat ducts secrete ~40-70 mM HCO ₃ ^-. 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 HCO ₃ ^- 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 ^-/HCO ₃ ^- 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 ^-/HCO ₃ ^- 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 HCO ₃ ^- secretion in species that share a high HCO ₃ ^- secretory output.

Original language	English
Pages (from-to)	C289-C303
Journal	American Journal of Physiology - Cell Physiology
Volume	301
Issue number	2
DOIs	https://doi.org/10.1152/ajpcell.00089.2011
Publication status	Published - 2011 Aug
Externally published	Yes

Keywords

Chloride
Oxalate
Slc26a11
Slc26a3
Slc26a6
Sulfate
Xenopus oocyte

ASJC Scopus subject areas

Physiology
Cell Biology

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10.1152/ajpcell.00089.2011

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title = "SLC26 anion exchangers of guinea pig pancreatic duct: Molecular cloning and functional characterization",

abstract = "The secretin-stimulated human pancreatic duct secretes HCO - 3 -rich fluid essential for normal digestion. Optimal stimulation of pancreatic HCO - 3 secretion likely requires coupled activities of the cystic fibrosis transmembrane regulator (CFTR) anion channel and apical SLC26 Cl -/HCO 3 - exchangers. However, whereas stimulated human and guinea pig pancreatic ducts secrete -140 mM HCO 3 - or more, mouse and rat ducts secrete ~40-70 mM HCO 3 -. 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 HCO 3 - 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 -/HCO 3 - 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 -/HCO 3 - 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 HCO 3 - secretion in species that share a high HCO 3 - secretory output.",

keywords = "Chloride, Oxalate, Slc26a11, Slc26a3, Slc26a6, Sulfate, Xenopus oocyte",

author = "Stewart, {Andrew K.} and Shmukler, {Boris E.} and Vandorpe, {David H.} and Fabian Reimold and Heneghan, {John F.} and M. Nakakuki and Arash Akhavein and Shigeru Ko and Hiroshi Ishiguro and Alper, {Seth L.}",

year = "2011",

month = aug,

doi = "10.1152/ajpcell.00089.2011",

language = "English",

volume = "301",

pages = "C289--C303",

journal = "American Journal of Physiology - Cell Physiology",

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T1 - SLC26 anion exchangers of guinea pig pancreatic duct

T2 - Molecular cloning and functional characterization

AU - Stewart, Andrew K.

AU - Shmukler, Boris E.

AU - Vandorpe, David H.

AU - Reimold, Fabian

AU - Heneghan, John F.

AU - Nakakuki, M.

AU - Akhavein, Arash

AU - Ko, Shigeru

AU - Ishiguro, Hiroshi

AU - Alper, Seth L.

PY - 2011/8

Y1 - 2011/8

N2 - The secretin-stimulated human pancreatic duct secretes HCO - 3 -rich fluid essential for normal digestion. Optimal stimulation of pancreatic HCO - 3 secretion likely requires coupled activities of the cystic fibrosis transmembrane regulator (CFTR) anion channel and apical SLC26 Cl -/HCO 3 - exchangers. However, whereas stimulated human and guinea pig pancreatic ducts secrete -140 mM HCO 3 - or more, mouse and rat ducts secrete ~40-70 mM HCO 3 -. 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 HCO 3 - 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 -/HCO 3 - 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 -/HCO 3 - 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 HCO 3 - secretion in species that share a high HCO 3 - secretory output.

AB - The secretin-stimulated human pancreatic duct secretes HCO - 3 -rich fluid essential for normal digestion. Optimal stimulation of pancreatic HCO - 3 secretion likely requires coupled activities of the cystic fibrosis transmembrane regulator (CFTR) anion channel and apical SLC26 Cl -/HCO 3 - exchangers. However, whereas stimulated human and guinea pig pancreatic ducts secrete -140 mM HCO 3 - or more, mouse and rat ducts secrete ~40-70 mM HCO 3 -. 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 HCO 3 - 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 -/HCO 3 - 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 -/HCO 3 - 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 HCO 3 - secretion in species that share a high HCO 3 - secretory output.

KW - Chloride

KW - Oxalate

KW - Slc26a11

KW - Slc26a3

KW - Slc26a6

KW - Sulfate

KW - Xenopus oocyte

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DO - 10.1152/ajpcell.00089.2011

M3 - Article

C2 - 21593449

AN - SCOPUS:79961008681

SN - 0363-6143

VL - 301

SP - C289-C303

JO - American Journal of Physiology - Cell Physiology

JF - American Journal of Physiology - Cell Physiology

IS - 2

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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