KEGG   PATHWAY: ko04972
Entry
ko04972                     Pathway                                

Name
Pancreatic secretion
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
ko04972  Pancreatic secretion
ko04972

Other DBs
GO: 0030157
Orthology
K04131  muscarinic acetylcholine receptor M3
K05226  cholecystokinin
K04194  cholecystokinin A receptor
K04634  guanine nucleotide-binding protein G(q) subunit alpha
K05858  phosphatidylinositol phospholipase C, beta [EC:3.1.4.11]
K02677  classical protein kinase C alpha type [EC:2.7.11.13]
K19662  classical protein kinase C beta type [EC:2.7.11.13]
K19663  classical protein kinase C gamma type [EC:2.7.11.13]
K07884  Ras-related protein Rab-3D
K07901  Ras-related protein Rab-8A
K07904  Ras-related protein Rab-11A
K07886  Ras-related protein Rab-27B
K04353  Ras-related protein Rap-1A
K07836  Ras-related protein Rap-1B
K04513  Ras homolog gene family, member A
K04392  Ras-related C3 botulinum toxin substrate 1
K01176  alpha-amylase [EC:3.2.1.1]
K01312  trypsin [EC:3.4.21.4]
K01310  chymotrypsin [EC:3.4.21.1]
K09632  chymotrypsin-like protease [EC:3.4.21.-]
K01346  pancreatic elastase II [EC:3.4.21.71]
K01345  pancreatic endopeptidase E [EC:3.4.21.70]
K08779  carboxypeptidase A1 [EC:3.4.17.1]
K01298  carboxypeptidase A2 [EC:3.4.17.15]
K08780  carboxypeptidase A3 [EC:3.4.17.1]
K01291  carboxypeptidase B [EC:3.4.17.2]
K01300  carboxypeptidase B2 [EC:3.4.17.20]
K14073  pancreatic triacylglycerol lipase [EC:3.1.1.3]
K14074  pancreatic lipase-related protein 1 [EC:3.1.1.3]
K14075  pancreatic lipase-related protein 2 [EC:3.1.1.3]
K12298  bile salt-stimulated lipase [EC:3.1.1.13 3.1.1.3]
K01047  secretory phospholipase A2 [EC:3.1.1.4]
K04958  inositol 1,4,5-triphosphate receptor type 1
K04959  inositol 1,4,5-triphosphate receptor type 2
K04960  inositol 1,4,5-triphosphate receptor type 3
K04962  ryanodine receptor 2
K01242  ADP-ribosyl cyclase 1 [EC:3.2.2.6 2.4.99.20]
K18152  ADP-ribosyl cyclase 2 [EC:3.2.2.6 2.4.99.20]
K14077  two pore calcium channel protein 2
K05853  P-type Ca2+ transporter type 2A [EC:7.2.2.10]
K05027  calcium-activated chloride channel regulator 1
K05028  calcium-activated chloride channel regulator 2
K05030  calcium-activated chloride channel regulator 3/4
K04964  transient receptor potential cation channel subfamily C member 1
K10951  solute carrier family 12 (sodium/potassium/chloride transporter), member 2
K01539  sodium/potassium-transporting ATPase subunit alpha [EC:7.2.2.13]
K01540  sodium/potassium-transporting ATPase subunit beta
K01538  sodium/potassium-transporting ATPase subunit gamma (FXYD domain-containing ion transport regulator 2)
K04926  potassium voltage-gated channel KQT-like subfamily member 1
K04936  potassium large conductance calcium-activated channel subfamily M alpha member 1
K05850  P-type Ca2+ transporter type 2B [EC:7.2.2.10]
K05742  solute carrier family 9 (sodium/hydrogen exchanger), member 1
K13855  solute carrier family 4 (anion exchanger), member 2
K05263  secretin
K04588  secretin receptor
K04632  guanine nucleotide-binding protein G(s) subunit alpha
K08041  adenylate cyclase 1 [EC:4.6.1.1]
K08042  adenylate cyclase 2 [EC:4.6.1.1]
K08043  adenylate cyclase 3 [EC:4.6.1.1]
K08044  adenylate cyclase 4 [EC:4.6.1.1]
K08045  adenylate cyclase 5 [EC:4.6.1.1]
K08046  adenylate cyclase 6 [EC:4.6.1.1]
K08047  adenylate cyclase 7 [EC:4.6.1.1]
K08048  adenylate cyclase 8 [EC:4.6.1.1]
K08049  adenylate cyclase 9 [EC:4.6.1.1]
K05031  cystic fibrosis transmembrane conductance regulator [EC:5.6.1.6]
K14078  solute carrier family 26 (chloride anion exchanger), member 3
K13575  solute carrier family 4 (sodium bicarbonate cotransporter), member 4
K18245  carbonic anhydrase 2 [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
ko04020  Calcium signaling pathway
ko04530  Tight junction
ko04973  Carbohydrate digestion and absorption
ko04974  Protein digestion and absorption
ko04975  Fat digestion and absorption
ko04977  Vitamin digestion and absorption

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