KEGG   PATHWAY: vvp04972
Entry
vvp04972                    Pathway                                
Name
Pancreatic secretion - Vulpes vulpes (red fox)
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
vvp04972  Pancreatic secretion
vvp04972

Other DBs
GO: 0030157
Organism
Vulpes vulpes (red fox) [GN:vvp]
Gene
112927380  CHRM3; muscarinic acetylcholine receptor M3 [KO:K04131]
112921523  CCK; cholecystokinin [KO:K05226]
112919087  CCKAR; cholecystokinin receptor type A isoform X1 [KO:K04194]
112922087  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
112924037  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
112930053  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
112930054  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
112919942  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
112920728  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
112908300  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
112909321  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
112908093  RAB3D; ras-related protein Rab-3D [KO:K07884]
112913135  RAB8A; ras-related protein Rab-8A [KO:K07901]
112928467  RAB11A; ras-related protein Rab-11A [KO:K07904]
112919279  RAB27B; ras-related protein Rab-27B [KO:K07886]
112907935  RAP1A; ras-related protein Rap-1A [KO:K04353]
112922290  RAP1B; ras-related protein Rap-1b [KO:K07836]
112911519  RHOA; transforming protein RhoA [KO:K04513]
112910012  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
112918226  pancreatic alpha-amylase [KO:K01176] [EC:3.2.1.1]
112907070  cationic trypsin [KO:K01312] [EC:3.4.21.4]
112907029  anionic trypsin [KO:K01312] [EC:3.4.21.4]
112915848  chymotrypsinogen 2-like [KO:K01310] [EC:3.4.21.1]
112915850  chymotrypsinogen 2 [KO:K01310] [EC:3.4.21.1]
112929441  CTRL; chymotrypsin-like protease CTRL-1 [KO:K09632] [EC:3.4.21.-]
112929845  CELA3B; chymotrypsin-like elastase family member 3B [KO:K01345] [EC:3.4.21.70]
112929000  CPA1; carboxypeptidase A1 [KO:K08779] [EC:3.4.17.1]
112932789  CPA3; mast cell carboxypeptidase A [KO:K08780] [EC:3.4.17.1]
112932756  CPB1; carboxypeptidase B [KO:K01291] [EC:3.4.17.2]
112933941  CPB2; carboxypeptidase B2 [KO:K01300] [EC:3.4.17.20]
112917878  pancreatic triacylglycerol lipase isoform X1 [KO:K14073] [EC:3.1.1.3]
112917885  inactive pancreatic lipase-related protein 1 [KO:K14074] [EC:3.1.1.3]
112917892  LOW QUALITY PROTEIN: pancreatic lipase-related protein 2-like [KO:K14075] [EC:3.1.1.3]
112928007  CEL; bile salt-activated lipase [KO:K12298] [EC:3.1.1.13 3.1.1.3]
112928381  PLA2G12B; group XIIB secretory phospholipase A2-like protein isoform X1 [KO:K01047] [EC:3.1.1.4]
112923229  group 10 secretory phospholipase A2-like [KO:K01047] [EC:3.1.1.4]
112909864  PLA2G3; LOW QUALITY PROTEIN: group 3 secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
112929714  PLA2G2D; group IID secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
112929718  PLA2G2F; group IIF secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
112929725  group IIE secretory phospholipase A2-like [KO:K01047] [EC:3.1.1.4]
112929819  PLA2G5; calcium-dependent phospholipase A2 isoform X1 [KO:K01047] [EC:3.1.1.4]
112929821  PLA2G2C; putative inactive group IIC secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
112934210  PLA2G12A; group XIIA secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
112932930  PLA2G1B; phospholipase A2 [KO:K01047] [EC:3.1.1.4]
112913302  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
112917203  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
112913900  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
112927407  RYR2; ryanodine receptor 2 [KO:K04962]
112919984  CD38; ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 [KO:K01242] [EC:3.2.2.6 2.4.99.20]
112919977  BST1; ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2 [KO:K18152] [EC:3.2.2.6 2.4.99.20]
112924016  TPCN2; two pore calcium channel protein 2 [KO:K14077]
112935193  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
112911398  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X1 [KO:K05853] [EC:7.2.2.10]
112929189  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X1 [KO:K05853] [EC:7.2.2.10]
112924417  CLCA1; calcium-activated chloride channel regulator 1 [KO:K05027]
112924440  CLCA2; calcium-activated chloride channel regulator 2 [KO:K05028]
112924418  CLCA4; calcium-activated chloride channel regulator 4 [KO:K05030]
112924442  calcium-activated chloride channel regulator 1-like [KO:K05030]
112934962  TRPC1; short transient receptor potential channel 1 isoform X1 [KO:K04964]
112917101  SLC12A2; solute carrier family 12 member 2 [KO:K10951]
112916773  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
112931443  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 [KO:K01539] [EC:7.2.2.13]
112910077  sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
112910081  sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
112924852  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
112923490  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
112934460  ATP1B4; protein ATP1B4 isoform X1 [KO:K01540]
112934973  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
112920357  FXYD2; sodium/potassium-transporting ATPase subunit gamma isoform X1 [KO:K01538]
112924005  KCNQ1; potassium voltage-gated channel subfamily KQT member 1 [KO:K04926]
112924709  KCNMA1; calcium-activated potassium channel subunit alpha-1 isoform X1 [KO:K04936]
112933678  plasma membrane calcium-transporting ATPase 2 [KO:K05850] [EC:7.2.2.10]
112911488  ATP2B3; plasma membrane calcium-transporting ATPase 3 isoform X1 [KO:K05850] [EC:7.2.2.10]
112914901  ATP2B1; plasma membrane calcium-transporting ATPase 1 isoform X1 [KO:K05850] [EC:7.2.2.10]
112914411  ATP2B4; plasma membrane calcium-transporting ATPase 4 isoform X1 [KO:K05850] [EC:7.2.2.10]
112931659  SLC9A1; sodium/hydrogen exchanger 1 [KO:K05742]
112916213  SLC4A2; anion exchange protein 2 isoform X1 [KO:K13855]
112934322  SCTR; secretin receptor isoform X1 [KO:K04588]
112932168  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
112932169  neuroendocrine secretory protein 55 [KO:K04632]
112911455  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
112934273  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
112908545  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
112926558  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
112913504  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
112921089  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
112929565  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
112915982  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
112923266  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
112929896  CFTR; cystic fibrosis transmembrane conductance regulator [KO:K05031] [EC:5.6.1.6]
112908576  SLC26A3; chloride anion exchanger [KO:K14078]
112909252  electrogenic sodium bicarbonate cotransporter 1 isoform X1 [KO:K13575]
112931543  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
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
vvp04020  Calcium signaling pathway
vvp04530  Tight junction
vvp04973  Carbohydrate digestion and absorption
vvp04974  Protein digestion and absorption
vvp04975  Fat digestion and absorption
vvp04977  Vitamin digestion and absorption
KO pathway
ko04972   
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