title: The cystic fibrosis of exocrine pancreas.
abstract: The cystic fibrosis transmembrane conductance regulator (CFTR) protein is highly expressed in the pancreatic duct epithelia and permits anions and water to enter the ductal lumen. This results in an increased volume of alkaline fluid allowing the highly concentrated proteins secreted by the acinar cells to remain in a soluble state. This work will expound on the pathophysiology and pathology caused by the malfunctioning CFTR protein with special reference to ion transport and acid-base abnormalities both in humans and animal models. We will also discuss the relationship between cystic fibrosis (CF) and pancreatitis, and outline present and potential therapeutic approaches in CF treatment relevant to the pancreas.
authors: Pediatric Gastroenterology, Hadassah University Hospital, Jerusalem 91240, Israel.
authors: Michael
authors: M
authors: Wilschanski
authors: Ivana
authors: I
authors: Novak
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D018118:Chloride Channels / Q000502:physiology; D003550:Cystic Fibrosis / Q000150:complications* / Q000378:metabolism / Q000628:therapy; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004195:Disease Models, Animal; D004386:Duodenum / Q000737:chemistry; D005289:Ferrets; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport / Q000502:physiology; D051379:Mice; D009154:Mutation / Q000502:physiology; D046790:Pancreas, Exocrine / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D010183:Pancreatic Ducts / Q000378:metabolism; D010195:Pancreatitis / Q000209:etiology* / Q000628:therapy; D019518:Postprandial Period; D015221:Potassium Channels / Q000502:physiology; D017494:Proton Pumps / Q000502:physiology; D012008:Recurrence; D013552:Swine
chemical_list: D001639:Bicarbonates; C505032:CFTR protein, human; D018118:Chloride Channels; D015221:Potassium Channels; D017494:Proton Pumps; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
references: J Pediatr Gastroenterol Nutr. 1982;1(4):559-65
references: 7186068
references: Pflugers Arch. 1993 Aug;424(3-4):315-20
references: 8414920
references: J Physiol. 2010 Sep 15;588(Pt 18):3615-27
references: 20643770
references: Gastroenterology. 1995 Mar;108(3):850-9
references: 7875488
references: J Physiol. 1998 Sep 1;511 ( Pt 2):407-22
references: 9706019
references: Science. 1989 Sep 8;245(4922):1066-73
references: 2475911
references: Acta Physiol (Oxf). 2011 Jul;202(3):501-22
references: 21073662
references: Br J Pharmacol. 2011 May;163(1):173-83
references: 21108631
references: Pflugers Arch. 1995 May;430(1):26-33
references: 7545279
references: J Clin Invest. 2010 Sep;120(9):3149-60
references: 20739752
references: Pediatr Res. 1996 Aug;40(2):242-9
references: 8827772
references: Lancet. 2008 Aug 2;372(9636):415-7
references: 18675692
references: Nature. 1991 Aug 15;352(6336):628-31
references: 1714039
references: Curr Gastroenterol Rep. 2010 Dec;12(6):458-64
references: 20821079
references: J Clin Invest. 2009 Jan;119(1):193-202
references: 19033647
references: J Physiol. 2006 Oct 1;576(Pt 1):163-78
references: 16857709
references: N Engl J Med. 1998 Sep 3;339(10):653-8
references: 9725922
references: Dig Dis Sci. 1990 Oct;35(10):1299-304
references: 2120019
references: J Clin Invest. 2011 Mar;121(3):956-65
references: 21317537
references: Am J Physiol Gastrointest Liver Physiol. 2010 Aug;299(2):G400-12
references: 20522641
references: Physiology (Bethesda). 2007 Oct;22:335-41
references: 17928547
references: Chest. 2007 Nov;132(5):1631-6
references: 17998363
references: Biochim Biophys Acta. 2002 Nov 13;1566(1-2):162-8
references: 12421547
references: Gut. 2003 Jul;52(7):1008-16
references: 12801959
references: Curr Opin Pharmacol. 2009 Jun;9(3):262-7
references: 19285919
references: Pflugers Arch. 1991 Aug;419(1):76-83
references: 1945765
references: J Membr Biol. 1988 Oct;105(2):131-42
references: 2464063
references: Transgenic Res. 1992 Mar;1(2):101-5
references: 1284480
references: J Clin Invest. 1995 Oct;96(4):2051-64
references: 7560099
references: Pediatrics. 2005 Apr;115(4):e463-9
references: 15772171
references: Pflugers Arch. 1988 May;411(5):546-53
references: 2455270
references: EMBO J. 2006 Nov 1;25(21):5049-57
references: 17053783
references: J Physiol. 2001 Sep 15;535(Pt 3):795-807
references: 11559776
references: Genomics. 2000 Nov 15;70(1):102-12
references: 11087667
references: Endocrinology. 1997 Apr;138(4):1736-41
references: 9075738
references: Gastroenterology. 2004 Oct;127(4):1162-73
references: 15480994
references: Pediatrics. 1975 Jan;55(1):86-95
references: 1110867
references: Am J Physiol. 1994 Jan;266(1 Pt 1):C213-21
references: 7508188
references: N Engl J Med. 1985 Feb 7;312(6):329-34
references: 3969086
references: Pancreatology. 2001;1(4):320-35
references: 12120211
references: Am J Physiol. 1989 Aug;257(2 Pt 1):C240-51
references: 2475028
references: J Biol Chem. 2001 May 18;276(20):17236-43
references: 11278980
references: Biochem Biophys Res Commun. 1991 Oct 15;180(1):342-8
references: 1718277
references: APMIS. 2010 Dec;118(12):982-90
references: 21091780
references: Aliment Pharmacol Ther. 2006 Dec;24 Suppl 4:169-76
references: 17209861
references: J Clin Invest. 2009 Sep;119(9):2613-22
references: 19726884
references: EMBO J. 1996 Mar 1;15(5):955-63
references: 8605891
references: Am J Pathol. 2010 Mar;176(3):1377-89
references: 20110417
references: Hum Mol Genet. 1993 Oct;2(10):1561-9
references: 7505691
references: Am J Pathol. 2004 Apr;164(4):1481-93
references: 15039235
references: J Physiol. 1999 Sep 1;519 Pt 2:551-8
references: 10457070
references: Gastroenterology. 1983 Jul;85(1):40-5
references: 6303892
references: Am J Physiol Gastrointest Liver Physiol. 2001 Nov;281(5):G1301-8
references: 11668039
references: Nature. 2001 Mar 1;410(6824):94-7
references: 11242048
references: J Biol Chem. 2009 Oct 16;284(42):28698-703
references: 19679661
references: Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15370-5
references: 17873061
references: Eur J Pediatr. 2003 Nov;162(11):760-3
references: 13680386
references: J Biol Chem. 1999 May 21;274(21):14670-7
references: 10329661
references: Cold Spring Harb Perspect Med. 2013 Mar 01;3(3):a009522
references: 23457292
references: Annu Rev Nutr. 2008;28:55-72
references: 18498235
references: Am J Physiol Gastrointest Liver Physiol. 2007 Jan;292(1):G447-55
references: 16901991
references: J Physiol. 1975 Nov;252(2):379-96
references: 1206529
references: Science. 2008 Oct 24;322(5901):590-4
references: 18772398
references: Pflugers Arch. 1993 Oct;425(1-2):1-8
references: 7505913
references: Am J Physiol Gastrointest Liver Physiol. 2004 Aug;287(2):G480-90
references: 15064229
references: Pflugers Arch. 2009 Nov;459(1):203-14
references: 19655163
references: Am J Hum Genet. 1992 Jun;50(6):1178-84
references: 1376016
references: N Engl J Med. 1998 Sep 3;339(10):645-52
references: 9725921
references: Gastroenterology. 2010 Nov;139(5):1711-20, 1720.e1-5
references: 20691184
references: Am J Physiol Cell Physiol. 2003 Aug;285(2):C433-45
references: 12711595
references: J Membr Biol. 1998 Jul 15;164(2):155-67
references: 9662559
references: Gastroenterology. 1997 Sep;113(3):914-9
references: 9287984
references: Am J Physiol Gastrointest Liver Physiol. 2001 Oct;281(4):G899-906
references: 11557509
references: Pflugers Arch. 1994 Mar;426(5):412-8
references: 7517031
references: Am J Physiol Cell Physiol. 2013 Apr 1;304(7):C673-84
references: 23364268
references: Gastroenterology. 2001 Oct;121(4):950-7
references: 11606508
references: Eur J Med Res. 1997 Oct 30;2(10):431-6
references: 9348270
references: Nature. 2008 Oct 30;455(7217):1210-5
references: 18724360
references: Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):479-83
references: 7507247
references: J Gen Physiol. 1994 Jul;104(1):57-85
references: 7964596
references: Physiology (Bethesda). 2008 Apr;23:104-14
references: 18400693
references: Gastroenterology. 2010 Aug;139(2):620-31
references: 20398666
references: Hum Mol Genet. 2002 Feb 1;11(3):243-51
references: 11823443
references: Annu Rev Physiol. 2010;72:95-121
references: 19827947
references: Gastroenterology. 1981 Apr;80(4):796-9
references: 6781974
references: J Clin Invest. 2009 Sep;119(9):2535-7
references: 19726878
references: J Pediatr Gastroenterol Nutr. 1996 Jul;23(1):45-50
references: 8811523
references: J Physiol. 1996 Aug 15;495 ( Pt 1):169-78
references: 8866360
references: J Biol Chem. 1999 Nov 5;274(45):31784-91
references: 10542200
references: Gastroenterology. 2011 Jan;140(1):153-61
references: 20923678
references: Gastroenterology. 2011 Jan;140(1):162-71
references: 20977904
references: Proc Natl Acad Sci U S A. 2006 Jun 20;103(25):9542-7
references: 16769890
references: Cold Spring Harb Perspect Med. 2013 Jul 01;3(7):
references: 23818513
references: J Biol Chem. 1998 Jul 10;273(28):17689-95
references: 9651366
references: Science. 1992 Aug 21;257(5073):1083-8
references: 1380723
references: N Engl J Med. 1990 Nov 29;323(22):1517-22
references: 2233932
references: Cell. 2008 Sep 19;134(6):1019-29
references: 18805094
references: J Biol Chem. 2001 Aug 31;276(35):32925-32
references: 11387334
references: J Biol Chem. 2003 Jan 3;278(1):200-7
references: 12409301
references: Mamm Genome. 1994 Aug;5(8):465-72
references: 7949729
references: Hum Genet. 2005 Dec;118(3-4):372-81
references: 16193325
references: Am J Physiol. 1997 Jan;272(1 Pt 1):G124-34
references: 9038885
references: Pflugers Arch. 1998 May;435(6):796-803
references: 9518508
references: J Biol Chem. 2007 Mar 2;282(9):6068-74
references: 17178714
references: J Membr Biol. 1990 May;115(3):203-15
references: 1695685
references: J Cyst Fibros. 2009 Mar;8(2):115-21
references: 19019741
references: Am J Respir Crit Care Med. 2007 Aug 15;176(4):362-9
references: 17446337
references: Science. 2008 Sep 26;321(5897):1837-41
references: 18818360
references: Drugs. 2009 Oct 1;69(14):1903-10
references: 19747007
references: EMBO J. 1995 Sep 15;14(18):4403-11
references: 7556083
references: Gastroenterology. 2002 Dec;123(6):1857-64
references: 12454843
references: Biochem Biophys Res Commun. 2007 Feb 16;353(3):535-40
references: 17194447
references: Am J Physiol. 1998 Feb;274(2):G413-8
references: 9486197
references: Gastroenterology. 1988 Aug;95(2):349-55
references: 3391365
references: Scand J Gastroenterol. 1991 Oct;26(10):1035-41
references: 1947769
references: Purinergic Signal. 2008 Sep;4(3):237-53
references: 18368520
references: Protein Eng Des Sel. 2010 May;23(5):365-73
references: 20150178
references: Am J Physiol Gastrointest Liver Physiol. 2009 Jun;296(6):G1307-17
references: 19342507
references: Nat Genet. 1993 May;4(1):35-41
references: 7685652
references: J Biol Chem. 2011 Jan 7;286(1):280-9
references: 20978133
references: Am J Physiol. 1993 Mar;264(3 Pt 1):C591-602
references: 7681623
references: Gastroenterology. 2000 Jun;118(6):1187-96
references: 10833494
references: Am J Physiol. 1995 Apr;268(4 Pt 1):G717-23
references: 7537458
references: Pflugers Arch. 2005 Sep;450(6):429-36
references: 16075244
references: Pflugers Arch. 1988 Jan;411(1):58-68
references: 3353213
references: Am J Respir Crit Care Med. 2006 Oct 1;174(7):787-94
references: 16840743
references: Sci Transl Med. 2010 Apr 28;2(29):29ra31
references: 20427821
references: Gut. 2007 Aug;56(8):1153-63
references: 17446304
references: Am J Physiol Cell Physiol. 2012 Jul 15;303(2):C151-9
references: 22555847
references: Biochem J. 2010 Jul 15;429(2):303-11
references: 20441565
references: J Gen Physiol. 2010 May;135(5):527-43
references: 20421376
references: J Gen Physiol. 2009 Mar;133(3):315-26
references: 19204187
references: Gastroenterology. 2005 Aug;129(2):665-81
references: 16083720
references: J Clin Invest. 1991 Aug;88(2):712-6
references: 1713921
references: Science. 1989 Sep 8;245(4922):1073-80
references: 2570460
references: Pediatr Res. 1999 Apr;45(4 Pt 1):482-8
references: 10203138
references: J Physiol. 1996 Oct 1;496 ( Pt 1):265-73
references: 8910214