KEGG   PATHWAY: aml04972
Entry
aml04972                    Pathway                                
Name
Pancreatic secretion - Ailuropoda melanoleuca (giant panda)
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
aml04972  Pancreatic secretion
aml04972

Other DBs
GO: 0030157
Organism
Ailuropoda melanoleuca (giant panda) [GN:aml]
Gene
109488507  CHRM3; muscarinic acetylcholine receptor M3 isoform X1 [KO:K04131]
100477337  CCK; cholecystokinin [KO:K05226]
100471458  CCKAR; cholecystokinin receptor type A [KO:K04194]
100464853  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
100481755  PLCB1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
100480603  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
100465232  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
100474779  PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
100477326  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
100478007  PRKCB; protein kinase C beta type isoform X2 [KO:K19662] [EC:2.7.11.13]
100484719  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
100464077  RAB3D; ras-related protein Rab-3D isoform X1 [KO:K07884]
100471245  RAB8A; ras-related protein Rab-8A [KO:K07901]
100477283  RAB11A; ras-related protein Rab-11A [KO:K07904]
100465563  RAB27B; ras-related protein Rab-27B [KO:K07886]
100471801  RAP1A; ras-related protein Rap-1A [KO:K04353]
100480240  RAP1B; ras-related protein Rap-1b [KO:K07836]
100476723  RHOA; transforming protein RhoA [KO:K04513]
100465648  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
100465041  alpha-amylase 2B [KO:K01176] [EC:3.2.1.1]
100471781  cationic trypsin [KO:K01312] [EC:3.4.21.4]
100472031  anionic trypsin [KO:K01312] [EC:3.4.21.4]
100479949  chymotrypsinogen B [KO:K01310] [EC:3.4.21.1]
100478694  chymotrypsinogen B-like [KO:K01310] [EC:3.4.21.1]
100468578  CTRL; chymotrypsin-like protease CTRL-1 [KO:K09632] [EC:3.4.21.-]
100464577  proproteinase E isoform X2 [KO:K01345] [EC:3.4.21.70]
109488326  carboxypeptidase A1 isoform X1 [KO:K08779] [EC:3.4.17.1]
100478542  CPA2; carboxypeptidase A2 [KO:K01298] [EC:3.4.17.15]
100471713  CPA3; mast cell carboxypeptidase A [KO:K08780] [EC:3.4.17.1]
100471468  CPB1; carboxypeptidase B [KO:K01291] [EC:3.4.17.2]
100482734  CPB2; carboxypeptidase B2 [KO:K01300] [EC:3.4.17.20]
100471594  PNLIP; pancreatic triacylglycerol lipase [KO:K14073] [EC:3.1.1.3]
100470933  PNLIPRP1; inactive pancreatic lipase-related protein 1 [KO:K14074] [EC:3.1.1.3]
100471180  pancreatic lipase-related protein 2 isoform X2 [KO:K14075] [EC:3.1.1.3]
100472032  CEL; LOW QUALITY PROTEIN: bile salt-activated lipase [KO:K12298] [EC:3.1.1.13 3.1.1.3]
100484745  PLA2G5; calcium-dependent phospholipase A2 [KO:K01047] [EC:3.1.1.4]
100478212  PLA2G2E; group IIE secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
100463545  group IID secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
100463798  PLA2G2F; group IIF secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
100464051  PLA2G2C; putative inactive group IIC secretory phospholipase A2 isoform X1 [KO:K01047] [EC:3.1.1.4]
100471349  PLA2G10; group 10 secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
100479059  PLA2G3; group 3 secretory phospholipase A2 isoform X1 [KO:K01047] [EC:3.1.1.4]
100475358  PLA2G12A; group XIIA secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
100480927  PLA2G12B; group XIIB secretory phospholipase A2-like protein isoform X1 [KO:K01047] [EC:3.1.1.4]
100473488  PLA2G1B; phospholipase A2 [KO:K01047] [EC:3.1.1.4]
117796269  PLA2G2D; group IID secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
100467161  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X8 [KO:K04958]
100477888  ITPR2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
100471747  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
100476576  RYR2; LOW QUALITY PROTEIN: ryanodine receptor 2 [KO:K04962]
100481326  CD38; ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 [KO:K01242] [EC:3.2.2.6 2.4.99.20]
100463977  BST1; ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2 isoform X1 [KO:K18152] [EC:3.2.2.6 2.4.99.20]
100473327  TPCN2; two pore calcium channel protein 2 isoform X1 [KO:K14077]
100465699  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X6 [KO:K05853] [EC:7.2.2.10]
100470716  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X1 [KO:K05853] [EC:7.2.2.10]
100465047  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
100471019  calcium-activated chloride channel regulator 1 [KO:K05027]
100471268  CLCA2; calcium-activated chloride channel regulator 2 [KO:K05028]
100470767  CLCA4; calcium-activated chloride channel regulator 4 [KO:K05030]
100478635  calcium-activated chloride channel regulator 1 [KO:K05030]
100465650  short transient receptor potential channel 1 [KO:K04964]
100464321  SLC12A2; solute carrier family 12 member 2 [KO:K10951]
100477989  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 isoform X1 [KO:K01539] [EC:7.2.2.13]
100480641  sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
100480890  ATP1A4; sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
100477585  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 isoform X1 [KO:K01539] [EC:7.2.2.13]
100484596  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
100469080  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
100481012  ATP1B4; protein ATP1B4 isoform X3 [KO:K01540]
100468266  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
100469796  sodium/potassium-transporting ATPase subunit gamma isoform X1 [KO:K01538]
100466988  KCNQ1; potassium voltage-gated channel subfamily KQT member 1 [KO:K04926]
100473263  KCNMA1; calcium-activated potassium channel subunit alpha-1 isoform X23 [KO:K04936]
100472949  ATP2B2; plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:7.2.2.10]
100476768  ATP2B3; plasma membrane calcium-transporting ATPase 3 isoform X1 [KO:K05850] [EC:7.2.2.10]
100465354  ATP2B1; plasma membrane calcium-transporting ATPase 1 isoform X1 [KO:K05850] [EC:7.2.2.10]
100484762  ATP2B4; plasma membrane calcium-transporting ATPase 4 isoform X1 [KO:K05850] [EC:7.2.2.10]
100478707  SLC9A1; sodium/hydrogen exchanger 1 [KO:K05742]
100483077  SLC4A2; anion exchange protein 2 [KO:K13855]
100482998  SCTR; secretin receptor isoform X1 [KO:K04588]
100473680  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
100469231  neuroendocrine secretory protein 55 [KO:K04632]
100472777  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
100473195  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
100471164  ADCY3; adenylate cyclase type 3 isoform X2 [KO:K08043] [EC:4.6.1.1]
100471940  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
100482519  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
100476922  ADCY6; adenylate cyclase type 6 isoform X2 [KO:K08046] [EC:4.6.1.1]
100466965  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
100474121  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
100476495  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
100478723  CFTR; cystic fibrosis transmembrane conductance regulator [KO:K05031] [EC:5.6.1.6]
100472077  SLC26A3; chloride anion exchanger [KO:K14078]
100482348  SLC4A4; electrogenic sodium bicarbonate cotransporter 1 isoform X1 [KO:K13575]
100474697  CA2; carbonic anhydrase 2 isoform X2 [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
PMID:17850212
  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
PMID:20625287
  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
PMID:16891880
  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
PMID:15689674
  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
PMID:14660554
  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
PMID:18626068
  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
PMID:14637169
  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
PMID:16888148
  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
PMID:16930743
  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
PMID:15709963
  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
PMID:20224219
  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
PMID:17205399
  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
PMID:10835353
  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
PMID:10078532
  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
PMID:11087843
  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
PMID:19088252
  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
aml04020  Calcium signaling pathway
aml04530  Tight junction
aml04973  Carbohydrate digestion and absorption
aml04974  Protein digestion and absorption
aml04975  Fat digestion and absorption
aml04977  Vitamin digestion and absorption
KO pathway
ko04972   
LinkDB

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