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(-)/HCO(3)(-) 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 (36)Cl(-) 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.
authors: Renal Division and Vascular Biology Center, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
authors: Andrew K
authors: AK
authors: Stewart
authors: Boris E
authors: BE
authors: Shmukler
authors: David H
authors: DH
authors: Vandorpe
authors: Fabian
authors: F
authors: Reimold
authors: John F
authors: JF
authors: Heneghan
authors: M
authors: M
authors: Nakakuki
authors: Arash
authors: A
authors: Akhavein
authors: Shigeru
authors: S
authors: Ko
authors: Hiroshi
authors: H
authors: Ishiguro
authors: Seth L
authors: SL
authors: Alper
references: Gastroenterology. 2009 Mar;136(3):893-901
references: 19121635
references: Structure. 2010 Nov 10;18(11):1450-62
references: 21070944
references: Gene. 2003 May 22;310:143-9
references: 12801641
references: Am J Physiol Cell Physiol. 2001 Oct;281(4):C1344-54
references: 11546673
references: J Gen Physiol. 2011 Feb;137(2):239-51
references: 21282402
references: J Physiol. 2007 Oct 1;584(Pt 1):59-73
references: 17690150
references: J Physiol. 2003 May 15;549(Pt 1):3-19
references: 12651923
references: Proteomics. 2010 Nov;10(22):4053-76
references: 20957757
references: EMBO J. 2005 Jul 20;24(14):2499-511
references: 15990874
references: J Gen Physiol. 2009 Mar;133(3):315-26
references: 19204187
references: Pancreas. 1989;4(2):204-9
references: 2474164
references: Biochem J. 1999 Nov 15;344 Pt 1:221-9
references: 10548554
references: J Clin Invest. 2011 Mar;121(3):956-65
references: 21317537
references: Science. 2009 Jul 24;325(5939):473-7
references: 19556463
references: J Cell Biol. 1978 May;77(2):288-314
references: 649653
references: Neuroreport. 2001 Jul 3;12(9):1929-35
references: 11435925
references: J Gen Physiol. 2006 May;127(5):511-24
references: 16606687
references: Genomics. 2000 Nov 15;70(1):102-12
references: 11087667
references: J Cell Biol. 1971 Aug;50(2):469-83
references: 5112646
references: J Biol Chem. 1999 Feb 5;274(6):3414-21
references: 9920885
references: J Orthop Res. 2007 Sep;25(9):1145-53
references: 17474136
references: EMBO J. 2006 Nov 1;25(21):5049-57
references: 17053783
references: EMBO J. 1992 Aug;11(8):2863-7
references: 1639060
references: J Biol Chem. 1999 Aug 6;274(32):22855-61
references: 10428871
references: J Cell Physiol. 2008 Feb;214(2):442-55
references: 17654517
references: Am J Physiol Cell Physiol. 2009 Jun;296(6):C1279-90
references: 19321737
references: Gastroenterology. 2008 Nov;135(5):1645-1653.e3
references: 18930060
references: Nat Cell Biol. 2004 Apr;6(4):343-50
references: 15048129
references: Nat Genet. 2006 Apr;38(4):474-8
references: 16532010
references: Am J Physiol Gastrointest Liver Physiol. 2001 Nov;281(5):G1301-8
references: 11668039
references: Mol Membr Biol. 2010 Jan;27(1):12-22
references: 19951076
references: EMBO J. 2002 Nov 1;21(21):5662-72
references: 12411484
references: Annu Rev Physiol. 2005;67:377-409
references: 15709963
references: J Biol Chem. 1999 May 21;274(21):14670-7
references: 10329661
references: Am J Physiol Gastrointest Liver Physiol. 2007 Jan;292(1):G447-55
references: 16901991
references: Am J Physiol. 1992 Jul;263(1 Pt 1):C176-86
references: 1378996
references: Clin Exp Rheumatol. 1989 Nov-Dec;7(6):631-3
references: 2612083
references: Am J Physiol Cell Physiol. 2011 Feb;300(2):C276-86
references: 21068358
references: J Med Chem. 2009 Oct 22;52(20):6447-55
references: 19785436
references: J Physiol. 2008 Mar 1;586(5):1291-306
references: 18174209
references: Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8498-502
references: 7667318
references: Am J Physiol Gastrointest Liver Physiol. 2007 Apr;292(4):G1079-88
references: 17170027
references: Curr Opin Gastroenterol. 2009 Sep;25(5):447-53
references: 19571747
references: J Physiol. 1996 Aug 15;495 ( Pt 1):179-91
references: 8866361
references: Pediatr Dev Pathol. 2009 May-Jun;12(3):229-32
references: 19736658
references: Biochemistry. 1979 May 29;18(11):2210-8
references: 36128
references: Curr Biol. 2000 Jan 27;10(2):R53-5
references: 10662676
references: J Biol Chem. 2011 Mar 11;286(10):8534-8544
references: 21190940
references: Gastroenterology. 2010 Aug;139(2):620-31
references: 20398666
references: FASEB J. 2003 May;17(8):890-2
references: 12626430
references: J Gen Physiol. 1997 Mar;109(3):345-60
references: 9089441
references: J Mol Biol. 2010 Jul 16;400(3):448-62
references: 20471983
references: Biochim Biophys Acta. 1999 Jul 7;1454(2):174-82
references: 10381562
references: Am J Physiol Gastrointest Liver Physiol. 2009 Nov;297(5):G918-29
references: 20501439
references: Gastroenterol Clin North Am. 1990 Dec;19(4):873-93
references: 2269523
references: J Biol Chem. 2009 Mar 6;284(10):6126-39
references: 19103596
references: Mol Cell Proteomics. 2011 Apr;10(4):M110.006403
references: 21252268
references: Pflugers Arch. 2006 Jun;452(3):307-15
references: 16715296
references: Lab Anim. 1990 Apr;24(2):159-63
references: 2195234
references: Am J Physiol Gastrointest Liver Physiol. 2009 Jun;296(6):G1307-17
references: 19342507
references: Aging Cell. 2010 Apr;9(2):243-51
references: 20096033
references: J Biol Chem. 2005 Mar 4;280(9):8564-80
references: 15548529
references: Pflugers Arch. 2005 Feb;449(5):479-90
references: 15480750