KEGG   PATHWAY: hsa04972Help
Entry
hsa04972                    Pathway                                

Name
Pancreatic secretion - Homo sapiens (human)
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
hsa04972

All organismsOrtholog table
Disease
H00409  
Type II diabetes mellitus
H00933  
Hereditary pancreatitis
Drug
D00113  
Atropine (USP)
D00216  
Acarbose (JAN/USAN/INN)
D00525  
Pilocarpine (JAN/USP)
D00722  
Oxybutynin hydrochloride (JAN)
D01006  
Oxyphencyclimine hydrochloride (JAN)
D01148  
Tolterodine tartrate (JAN/USAN)
D01269  
Solifenacin succinate (JAN/USAN/INN)
D01323  
Azosemide (JAN/USAN/INN)
D01521  
Pipethanate hydrochloride (JAN)
D01634  
Piretanide (JAN/USAN/INN)
D01699  
Darifenacin hydrobromide (JAN/USAN)
D01818  
Proglumide (JP16/USAN/INN)
D01858  
Panazepide (JAN)
D01875  
Tiquizium bromide (JAN/INN)
D01929  
Tiotropium bromide hydrate (JAN)
D01946  
Oxitropium bromide (JAN/INN)
D01976  
N-Methylscopolamine methylsulfate (JAN)
D02021  
Secretin (JAN/USAN/INN)
D02069  
Atropine sulfate (JP16/USP)
D02070  
Homatropine methylbromide (USP)
D02200  
Pilocarpine hydrochloride (JP16/USP)
D02693  
Devazepide (USAN/INN)
D02710  
Tarazepide (INN)
D02876  
Alvameline maleate (USAN)
D03654  
Darifenacin (USAN/INN)
D03711  
Dexetimide (USAN/INN)
D04028  
Orlistat (USAN/INN)
D04057  
Esoxybutynin chloride (USAN)
D04970  
Methacholine chloride (USAN/INN)
D05183  
Ulinastatin (JP16)
D05478  
Pilocarpine nitrate (USP)
D06273  
Imidafenacin (JAN/INN)
D07076  
Camylofin (INN)
D07099  
Cimetropium bromide (INN)
D07667  
Cevimeline (INN)
D08325  
Oxyphencyclimine (INN)
D08376  
Pilocarpine borate
D08382  
Piperidolate (INN)
D08522  
Solifenacin (INN)
D08639  
Trimebutine (INN)
D09752  
Carpronium chloride hydrate (JAN)
D10134  
Lumacaftor (USAN)
Other DBs
BSID: 
GO: 
Organism
Homo sapiens (human) [GN:hsa]
Gene
1131  
CHRM3; cholinergic receptor, muscarinic 3 [KO:K04131]
886  
CCKAR; cholecystokinin A receptor [KO:K04194]
2776  
GNAQ; guanine nucleotide binding protein (G protein), q polypeptide [KO:K04634]
23236  
PLCB1; phospholipase C, beta 1 (phosphoinositide-specific) [KO:K05858] [EC:3.1.4.11]
5330  
PLCB2; phospholipase C, beta 2 [KO:K05858] [EC:3.1.4.11]
5331  
PLCB3; phospholipase C, beta 3 (phosphatidylinositol-specific) [KO:K05858] [EC:3.1.4.11]
5332  
PLCB4; phospholipase C, beta 4 [KO:K05858] [EC:3.1.4.11]
5578  
PRKCA; protein kinase C, alpha [KO:K02677] [EC:2.7.11.13]
5579  
PRKCB; protein kinase C, beta [KO:K02677] [EC:2.7.11.13]
5582  
PRKCG; protein kinase C, gamma [KO:K02677] [EC:2.7.11.13]
9545  
RAB3D; RAB3D, member RAS oncogene family [KO:K07884]
4218  
RAB8A; RAB8A, member RAS oncogene family [KO:K07901]
8766  
RAB11A; RAB11A, member RAS oncogene family [KO:K07904]
5874  
RAB27B; RAB27B, member RAS oncogene family [KO:K07886]
5906  
RAP1A; RAP1A, member of RAS oncogene family [KO:K04353]
5908  
RAP1B; RAP1B, member of RAS oncogene family [KO:K07836]
387  
RHOA; ras homolog family member A [KO:K04513]
5879  
RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
5646  
PRSS3; protease, serine, 3 [KO:K01312] [EC:3.4.21.4]
5645  
PRSS2; protease, serine, 2 (trypsin 2) [KO:K01312] [EC:3.4.21.4]
5644  
PRSS1; protease, serine, 1 (trypsin 1) [KO:K01312] [EC:3.4.21.4]
1506  
CTRL; chymotrypsin-like [KO:K09632] [EC:3.4.21.-]
63036  
CELA2A; chymotrypsin-like elastase family, member 2A [KO:K01346] [EC:3.4.21.71]
51032  
CELA2B; chymotrypsin-like elastase family, member 2B [KO:K01346] [EC:3.4.21.71]
10136  
CELA3A; chymotrypsin-like elastase family, member 3A [KO:K01345] [EC:3.4.21.70]
23436  
CELA3B; chymotrypsin-like elastase family, member 3B [KO:K01345] [EC:3.4.21.70]
1357  
CPA1; carboxypeptidase A1 (pancreatic) [KO:K08779] [EC:3.4.17.1]
1358  
CPA2; carboxypeptidase A2 (pancreatic) [KO:K01298] [EC:3.4.17.15]
1359  
CPA3; carboxypeptidase A3 (mast cell) [KO:K08780] [EC:3.4.17.1]
1360  
CPB1; carboxypeptidase B1 (tissue) [KO:K01291] [EC:3.4.17.2]
1361  
CPB2; carboxypeptidase B2 (plasma) [KO:K01300] [EC:3.4.17.20]
5406  
PNLIP; pancreatic lipase [KO:K14073] [EC:3.1.1.3]
5407  
PNLIPRP1; pancreatic lipase-related protein 1 [KO:K14074] [EC:3.1.1.3]
5408  
PNLIPRP2; pancreatic lipase-related protein 2 [KO:K14075] [EC:3.1.1.3]
1056  
CEL; carboxyl ester lipase [KO:K12298] [EC:3.1.1.3 3.1.1.13]
8399  
PLA2G10; phospholipase A2, group X [KO:K01047] [EC:3.1.1.4]
26279  
PLA2G2D; phospholipase A2, group IID [KO:K01047] [EC:3.1.1.4]
30814  
PLA2G2E; phospholipase A2, group IIE [KO:K01047] [EC:3.1.1.4]
50487  
PLA2G3; phospholipase A2, group III [KO:K01047] [EC:3.1.1.4]
64600  
PLA2G2F; phospholipase A2, group IIF [KO:K01047] [EC:3.1.1.4]
81579  
PLA2G12A; phospholipase A2, group XIIA [KO:K01047] [EC:3.1.1.4]
84647  
PLA2G12B; phospholipase A2, group XIIB [KO:K01047] [EC:3.1.1.4]
5319  
PLA2G1B; phospholipase A2, group IB (pancreas) [KO:K01047] [EC:3.1.1.4]
5322  
PLA2G5; phospholipase A2, group V [KO:K01047] [EC:3.1.1.4]
5320  
PLA2G2A; phospholipase A2, group IIA (platelets, synovial fluid) [KO:K01047] [EC:3.1.1.4]
391013  
PLA2G2C; phospholipase A2, group IIC [KO:K01047] [EC:3.1.1.4]
3708  
ITPR1; inositol 1,4,5-trisphosphate receptor, type 1 [KO:K04958]
3709  
ITPR2; inositol 1,4,5-trisphosphate receptor, type 2 [KO:K04959]
3710  
ITPR3; inositol 1,4,5-trisphosphate receptor, type 3 [KO:K04960]
6262  
RYR2; ryanodine receptor 2 (cardiac) [KO:K04962]
952  
CD38; CD38 molecule [KO:K01242] [EC:2.4.99.20 3.2.2.6]
683  
BST1; bone marrow stromal cell antigen 1 [KO:K18152] [EC:2.4.99.20 3.2.2.6]
219931  
TPCN2; two pore segment channel 2 [KO:K14077]
487  
ATP2A1; ATPase, Ca++ transporting, cardiac muscle, fast twitch 1 [KO:K05853] [EC:3.6.3.8]
489  
ATP2A3; ATPase, Ca++ transporting, ubiquitous [KO:K05853] [EC:3.6.3.8]
488  
ATP2A2; ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 [KO:K05853] [EC:3.6.3.8]
1179  
CLCA1; chloride channel accessory 1 [KO:K05027]
9635  
CLCA2; chloride channel accessory 2 [KO:K05028]
22802  
CLCA4; chloride channel accessory 4 [KO:K05030]
7220  
TRPC1; transient receptor potential cation channel, subfamily C, member 1 [KO:K04964]
6558  
SLC12A2; solute carrier family 12 (sodium/potassium/chloride transporter), member 2 [KO:K10951]
476  
ATP1A1; ATPase, Na+/K+ transporting, alpha 1 polypeptide [KO:K01539] [EC:3.6.3.9]
477  
ATP1A2; ATPase, Na+/K+ transporting, alpha 2 polypeptide [KO:K01539] [EC:3.6.3.9]
478  
ATP1A3; ATPase, Na+/K+ transporting, alpha 3 polypeptide [KO:K01539] [EC:3.6.3.9]
480  
ATP1A4; ATPase, Na+/K+ transporting, alpha 4 polypeptide [KO:K01539] [EC:3.6.3.9]
23439  
ATP1B4; ATPase, Na+/K+ transporting, beta 4 polypeptide [KO:K01540]
481  
ATP1B1; ATPase, Na+/K+ transporting, beta 1 polypeptide [KO:K01540]
482  
ATP1B2; ATPase, Na+/K+ transporting, beta 2 polypeptide [KO:K01540]
483  
ATP1B3; ATPase, Na+/K+ transporting, beta 3 polypeptide [KO:K01540]
486  
FXYD2; FXYD domain containing ion transport regulator 2 [KO:K01538]
3784  
KCNQ1; potassium voltage-gated channel, KQT-like subfamily, member 1 [KO:K04926]
3778  
KCNMA1; potassium large conductance calcium-activated channel, subfamily M, alpha member 1 [KO:K04936]
490  
ATP2B1; ATPase, Ca++ transporting, plasma membrane 1 [KO:K05850] [EC:3.6.3.8]
492  
ATP2B3; ATPase, Ca++ transporting, plasma membrane 3 [KO:K05850] [EC:3.6.3.8]
493  
ATP2B4; ATPase, Ca++ transporting, plasma membrane 4 [KO:K05850] [EC:3.6.3.8]
491  
ATP2B2; ATPase, Ca++ transporting, plasma membrane 2 [KO:K05850] [EC:3.6.3.8]
6548  
SLC9A1; solute carrier family 9, subfamily A (NHE1, cation proton antiporter 1), member 1 [KO:K05742]
6522  
SLC4A2; solute carrier family 4 (anion exchanger), member 2 [KO:K13855]
6344  
SCTR; secretin receptor [KO:K04588]
2778  
GNAS; GNAS complex locus [KO:K04632]
107  
ADCY1; adenylate cyclase 1 (brain) [KO:K08041] [EC:4.6.1.1]
108  
ADCY2; adenylate cyclase 2 (brain) [KO:K08042] [EC:4.6.1.1]
109  
ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
196883  
ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
111  
ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
112  
ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
113  
ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
114  
ADCY8; adenylate cyclase 8 (brain) [KO:K08048] [EC:4.6.1.1]
115  
ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
1080  
CFTR; cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7) [KO:K05031] [EC:3.6.3.49]
1811  
SLC26A3; solute carrier family 26 (anion exchanger), member 3 [KO:K14078]
8671  
SLC4A4; solute carrier family 4 (sodium bicarbonate cotransporter), member 4 [KO:K13575]
1504  
CTRB1; chymotrypsinogen B1 [KO:K01310] [EC:3.4.21.1]
279  
AMY2A; amylase, alpha 2A (pancreatic) [KO:K01176] [EC:3.2.1.1]
280  
AMY2B; amylase, alpha 2B (pancreatic) [KO:K01176] [EC:3.2.1.1]
760  
CA2; carbonic anhydrase II [KO:K01672] [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)
KO pathway
 

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