KEGG   PATHWAY: tup04972
Entry
tup04972                    Pathway                                

Name
Pancreatic secretion - Tupaia chinensis (Chinese tree shrew)
Description
The pancreas performs both exocrine and endocrine functions. The exocrine pancreas consists of two parts, the acinar and duct cells. The primary functions of pancreatic acinar cells are to synthesize and secrete digestive enzymes. Stimulation of the cell by secretagogues such as acetylcholine (ACh) and cholecystokinin (CCK) causes the generation of an intracellular Ca2+ signal. This signal, in turn, triggers the fusion of the zymogen granules with the apical plasma membrane, leading to the polarised secretion of the enzymes. The major task of pancreatic duct cells is the secretion of fluid and bicarbonate ions (HCO3-), which neutralize the acidity of gastric contents that enter the duodenum. An increase in intracellular cAMP by secretin is one of the major signals of pancreatic HCO3- secretion. Activation of the CFTR Cl- channel and the CFTR-dependent Cl-/HCO3- exchange activities is responsible for cAMP-induced HCO3- secretion.
Class
Organismal Systems; Digestive system
Pathway map
tup04972  Pancreatic secretion
tup04972

Other DBs
GO: 0030157
Organism
Tupaia chinensis (Chinese tree shrew) [GN:tup]
Gene
102488209  CHRM3; cholinergic receptor muscarinic 3 [KO:K04131]
102473848  CCK; cholecystokinin [KO:K05226]
102476506  CCKAR; cholecystokinin A receptor [KO:K04194]
102468263  GNAQ; G protein subunit alpha q [KO:K04634]
102477438  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
102476196  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
102472532  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
102492903  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
102495954  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
102469271  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
102497204  PRKCG; protein kinase C gamma [KO:K19663] [EC:2.7.11.13]
102481632  RAB3D; RAB3D, member RAS oncogene family [KO:K07884]
102481788  RAB8A; RAB8A, member RAS oncogene family [KO:K07901]
102489248  RAB11A; RAB11A, member RAS oncogene family [KO:K07904]
102472052  RAB27B; RAB27B, member RAS oncogene family [KO:K07886]
102475072  RAP1A; RAP1A, member of RAS oncogene family [KO:K04353]
102472381  RAP1B; RAP1B, member of RAS oncogene family [KO:K07836]
102487039  RHOA; ras homolog family member A [KO:K04513]
102479102  RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
102492959  AMY2A; pancreatic alpha-amylase [KO:K01176] [EC:3.2.1.1]
102497899  cationic trypsin-3 [KO:K01312] [EC:3.4.21.4]
102498709  PRSS2; protease, serine 2 [KO:K01312] [EC:3.4.21.4]
102489643  chymotrypsinogen B [KO:K01310] [EC:3.4.21.1]
102489237  CTRB1; chymotrypsinogen B [KO:K01310] [EC:3.4.21.1]
102474011  CTRL; chymotrypsin like [KO:K09632] [EC:3.4.21.-]
102494723  CELA2A; chymotrypsin-like elastase family member 2A [KO:K01346] [EC:3.4.21.71]
102489028  CELA3B; proproteinase E [KO:K01345] [EC:3.4.21.70]
102492627  CPA1; carboxypeptidase A1 [KO:K08779] [EC:3.4.17.1]
102489569  CPA2; carboxypeptidase A2 [KO:K01298] [EC:3.4.17.15]
102468722  CPA3; carboxypeptidase A3 [KO:K08780] [EC:3.4.17.1]
102469136  CPB1; carboxypeptidase B1 [KO:K01291] [EC:3.4.17.2]
102473098  CPB2; carboxypeptidase B2 [KO:K01300] [EC:3.4.17.20]
102491787  PNLIP; pancreatic lipase [KO:K14073] [EC:3.1.1.3]
102491370  PNLIPRP1; pancreatic lipase related protein 1 [KO:K14074] [EC:3.1.1.3]
102490957  PNLIPRP2; pancreatic lipase related protein 2 [KO:K14075] [EC:3.1.1.3]
102500820  CEL; carboxyl ester lipase [KO:K12298] [EC:3.1.1.13 3.1.1.3]
102497076  PLA2G5; phospholipase A2 group V [KO:K01047] [EC:3.1.1.4]
102496651  PLA2G2F; phospholipase A2 group IIF [KO:K01047] [EC:3.1.1.4]
102501355  PLA2G2D; phospholipase A2 group IID [KO:K01047] [EC:3.1.1.4]
102501775  PLA2G2A; phospholipase A2 group IIA [KO:K01047] [EC:3.1.1.4]
102502195  PLA2G2E; phospholipase A2 group IIE [KO:K01047] [EC:3.1.1.4]
102499549  PLA2G2C; phospholipase A2 group IIC [KO:K01047] [EC:3.1.1.4]
102475773  PLA2G3; phospholipase A2 group III [KO:K01047] [EC:3.1.1.4]
102476007  PLA2G10; group 10 secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
102501534  PLA2G1B; phospholipase A2 group IB [KO:K01047] [EC:3.1.1.4]
102480654  PLA2G12A; phospholipase A2 group XIIA [KO:K01047] [EC:3.1.1.4]
102488847  PLA2G12B; phospholipase A2 group XIIB [KO:K01047] [EC:3.1.1.4]
102473622  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
102482868  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
102475587  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102473653  RYR2; ryanodine receptor 2 [KO:K04962]
102480083  CD38; CD38 molecule [KO:K01242] [EC:3.2.2.6 2.4.99.20]
102468679  BST1; bone marrow stromal cell antigen 1 [KO:K18152] [EC:3.2.2.6 2.4.99.20]
102491632  TPCN2; two pore segment channel 2 [KO:K14077]
102499870  ATP2A1; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1 [KO:K05853] [EC:7.2.2.10]
102478604  ATP2A3; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3 [KO:K05853] [EC:7.2.2.10]
102497660  sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
106734944  sarcoplasmic/endoplasmic reticulum calcium ATPase 2-like [KO:K05853] [EC:7.2.2.10]
102496433  CLCA1; chloride channel accessory 1 [KO:K05027]
102491755  CLCA2; chloride channel accessory 2 [KO:K05028]
102495616  CLCA4; chloride channel accessory 4 [KO:K05030]
102480366  TRPC1; transient receptor potential cation channel subfamily C member 1 [KO:K04964]
102489962  SLC12A2; solute carrier family 12 member 2 [KO:K10951]
102475448  ATP1A3; ATPase Na+/K+ transporting subunit alpha 3 [KO:K01539] [EC:7.2.2.13]
102483255  ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
102483994  ATP1A1; ATPase Na+/K+ transporting subunit alpha 1 [KO:K01539] [EC:7.2.2.13]
102481090  ATP1B1; ATPase Na+/K+ transporting subunit beta 1 [KO:K01540]
102467892  ATP1B2; ATPase Na+/K+ transporting subunit beta 2 [KO:K01540]
102486693  ATP1B3; ATPase Na+/K+ transporting subunit beta 3 [KO:K01540]
102493344  sodium/potassium-transporting ATPase subunit beta-3-like [KO:K01540]
102474656  ATP1B4; ATPase Na+/K+ transporting family member beta 4 [KO:K01540]
102481218  FXYD2; FXYD domain containing ion transport regulator 2 [KO:K01538]
102500494  KCNQ1; potassium voltage-gated channel subfamily Q member 1 [KO:K04926]
102471296  KCNMA1; potassium calcium-activated channel subfamily M alpha 1 [KO:K04936]
102469597  ATP2B1; ATPase plasma membrane Ca2+ transporting 1 [KO:K05850] [EC:7.2.2.10]
102496553  ATP2B2; ATPase plasma membrane Ca2+ transporting 2 [KO:K05850] [EC:7.2.2.10]
102479920  ATP2B4; ATPase plasma membrane Ca2+ transporting 4 [KO:K05850] [EC:7.2.2.10]
102479023  ATP2B3; ATPase plasma membrane Ca2+ transporting 3 [KO:K05850] [EC:7.2.2.10]
102501147  SLC9A1; solute carrier family 9 member A1 [KO:K05742]
102497672  SLC4A2; solute carrier family 4 member 2 [KO:K13855]
102498510  SCTR; secretin receptor [KO:K04588]
102489563  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632]
102501321  neuroendocrine secretory protein 55 [KO:K04632]
102468873  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
102492353  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
102477532  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
102490273  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
102490639  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
102468478  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
102496578  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
102472317  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
102477344  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
102490714  CFTR; cystic fibrosis transmembrane conductance regulator [KO:K05031] [EC:5.6.1.6]
102470789  SLC26A3; solute carrier family 26 member 3 [KO:K14078]
102499824  SLC4A4; solute carrier family 4 member 4 [KO:K13575]
102489985  CA2; carbonic anhydrase 2 [KO:K18245] [EC:4.2.1.1]
Compound
C00001  H2O
C00011  CO2
C00076  Calcium cation
C00080  H+
C00165  Diacylglycerol
C00238  Potassium cation
C00288  HCO3-
C00575  3',5'-Cyclic AMP
C00698  Cl-
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
C01353  Carbonic acid
C01996  Acetylcholine
C13050  Cyclic ADP-ribose
C13051  Nicotinic acid adenine dinucleotide phosphate
Reference
  Authors
Petersen OH, Tepikin AV
  Title
Polarized calcium signaling in exocrine gland cells.
  Journal
Annu Rev Physiol 70:273-99 (2008)
DOI:10.1146/annurev.physiol.70.113006.100618
Reference
  Authors
Williams JA
  Title
Regulation of acinar cell function in the pancreas.
  Journal
Curr Opin Gastroenterol 26:478-83 (2010)
DOI:10.1097/MOG.0b013e32833d11c6
Reference
  Authors
Williams JA
  Title
Regulation of pancreatic acinar cell function.
  Journal
Curr Opin Gastroenterol 22:498-504 (2006)
DOI:10.1097/01.mog.0000239863.96833.c0
Reference
  Authors
Bi Y, Williams JA
  Title
Receptor biology and signal transduction in pancreatic acinar cells.
  Journal
Curr Opin Gastroenterol 20:427-34 (2004)
DOI:10.1097/00001574-200409000-00002
Reference
  Authors
Yamasaki M, Masgrau R, Morgan AJ, Churchill GC, Patel S, Ashcroft SJ, Galione A
  Title
Organelle selection determines agonist-specific Ca2+ signals in pancreatic acinar and beta cells.
  Journal
J Biol Chem 279:7234-40 (2004)
DOI:10.1074/jbc.M311088200
Reference
PMID:9548666
  Authors
Kanno T
  Title
Ca2+ signaling in the pancreatic acinus.
  Journal
Pancreas 16:273-6 (1998)
Reference
  Authors
Heitzmann D, Warth R
  Title
Physiology and pathophysiology of potassium channels in gastrointestinal epithelia.
  Journal
Physiol Rev 88:1119-82 (2008)
DOI:10.1152/physrev.00020.2007
Reference
  Authors
Konturek SJ, Zabielski R, Konturek JW, Czarnecki J
  Title
Neuroendocrinology of the pancreas; role of brain-gut axis in pancreatic secretion.
  Journal
Eur J Pharmacol 481:1-14 (2003)
DOI:10.1016/j.ejphar.2003.08.042
Reference
  Authors
Chu JY, Yung WH, Chow BK
  Title
Secretin: a pleiotrophic hormone.
  Journal
Ann N Y Acad Sci 1070:27-50 (2006)
DOI:10.1196/annals.1317.013
Reference
  Authors
Siu FK, Lam IP, Chu JY, Chow BK
  Title
Signaling mechanisms of secretin receptor.
  Journal
Regul Pept 137:95-104 (2006)
DOI:10.1016/j.regpep.2006.02.011
Reference
  Authors
Steward MC, Ishiguro H, Case RM
  Title
Mechanisms of bicarbonate secretion in the pancreatic duct.
  Journal
Annu Rev Physiol 67:377-409 (2005)
DOI:10.1146/annurev.physiol.67.031103.153247
Reference
  Authors
Kim D, Steward MC
  Title
The role of CFTR in bicarbonate secretion by pancreatic duct and airway epithelia.
  Journal
J Med Invest 56 Suppl:336-42 (2009)
DOI:10.2152/jmi.56.336
Reference
  Authors
Whitcomb DC, Lowe ME
  Title
Human pancreatic digestive enzymes.
  Journal
Dig Dis Sci 52:1-17 (2007)
DOI:10.1007/s10620-006-9589-z
Reference
  Authors
Cancela JM, Gerasimenko OV, Gerasimenko JV, Tepikin AV, Petersen OH
  Title
Two different but converging messenger pathways to intracellular Ca(2+) release: the roles of nicotinic acid adenine dinucleotide phosphate, cyclic ADP-ribose and inositol trisphosphate.
  Journal
EMBO J 19:2549-57 (2000)
DOI:10.1093/emboj/19.11.2549
Reference
  Authors
Cancela JM, Churchill GC, Galione A
  Title
Coordination of agonist-induced Ca2+-signalling patterns by NAADP in pancreatic acinar cells.
  Journal
Nature 398:74-6 (1999)
DOI:10.1038/18032
Reference
  Authors
Parekh AB
  Title
Calcium signaling and acute pancreatitis: specific response to a promiscuous messenger.
  Journal
Proc Natl Acad Sci U S A 97:12933-4 (2000)
DOI:10.1073/pnas.97.24.12933
Reference
  Authors
Williams JA, Chen X, Sabbatini ME
  Title
Small G proteins as key regulators of pancreatic digestive enzyme secretion.
  Journal
Am J Physiol Endocrinol Metab 296:E405-14 (2009)
DOI:10.1152/ajpendo.90874.2008
Related
pathway
tup04020  Calcium signaling pathway
tup04530  Tight junction
tup04973  Carbohydrate digestion and absorption
tup04974  Protein digestion and absorption
tup04975  Fat digestion and absorption
tup04977  Vitamin digestion and absorption
KO pathway
ko04972   
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