KEGG   PATHWAY: ko04972Help
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
BRITE hierarchy
Pathway map
Pancreatic secretion
ko04972

All organismsOrtholog table
Disease
H00409  
Type II diabetes mellitus
H00933  
Hereditary pancreatitis
Other DBs
BSID: 
GO: 
Orthology
K04131  
muscarinic acetylcholine receptor M3
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 [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
K01312  
trypsin [EC:3.4.21.4]
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:3.1.1.3 3.1.1.13]
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:2.4.99.20 3.2.2.6]
K18152  
ADP-ribosyl cyclase 2 [EC:2.4.99.20 3.2.2.6]
K14077  
two pore calcium channel protein 2
K05853  
Ca2+ transporting ATPase, sarcoplasmic/endoplasmic reticulum [EC:3.6.3.8]
K05027  
calcium-activated chloride channel regulator 1
K05028  
calcium-activated chloride channel regulator 2
K05030  
calcium-activated chloride channel regulator 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:3.6.3.9]
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  
Ca2+ transporting ATPase, plasma membrane [EC:3.6.3.8]
K05742  
solute carrier family 9 (sodium/hydrogen exchanger), member 1
K13855  
solute carrier family 4 (anion exchanger), member 2
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:3.6.3.49]
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
C13523  
Secretin
C16114  
Cholecystokinin-8
Reference
  Authors
Petersen OH, Tepikin AV
  Title
Polarized calcium signaling in exocrine gland cells.
  Journal
Annu Rev Physiol 70:273-99 (2008)
Reference
  Authors
Williams JA
  Title
Regulation of acinar cell function in the pancreas.
  Journal
Curr Opin Gastroenterol 26:478-83 (2010)
Reference
  Authors
Williams JA
  Title
Regulation of pancreatic acinar cell function.
  Journal
Curr Opin Gastroenterol 22:498-504 (2006)
Reference
  Authors
Bi Y, Williams JA
  Title
Receptor biology and signal transduction in pancreatic acinar cells.
  Journal
Curr Opin Gastroenterol 20:427-34 (2004)
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)
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)
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)
Reference
  Authors
Chu JY, Yung WH, Chow BK
  Title
Secretin: a pleiotrophic hormone.
  Journal
Ann N Y Acad Sci 1070:27-50 (2006)
Reference
  Authors
Siu FK, Lam IP, Chu JY, Chow BK
  Title
Signaling mechanisms of secretin receptor.
  Journal
Regul Pept 137:95-104 (2006)
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)
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)
Reference
  Authors
Whitcomb DC, Lowe ME
  Title
Human pancreatic digestive enzymes.
  Journal
Dig Dis Sci 52:1-17 (2007)
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)
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)
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)
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)

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