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KEGG   PATHWAY: hsa04972
hsa04972                    Pathway                                
Pancreatic secretion - Homo sapiens (human)
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.
Organismal Systems; Digestive system
Pathway map
hsa04972  Pancreatic secretion

D00216  Acarbose (JAN/USAN/INN)
D00717  Dicyclomine hydrochloride (JAN/USP)
D01006  Oxyphencyclimine hydrochloride (JAN)
D01113  Loxiglumide (JAN/INN)
D01165  Piperidolate hydrochloride (JAN)
D01297  Pirenzepine hydrochloride (USAN)
D01323  Azosemide (JP18/USAN/INN)
D01491  Butropium bromide (JP18/INN)
D01955  Aclatonium napadisilate (JAN)
D02021  Secretin (JAN/USAN/INN)
D02535  Timepidium bromide hydrate (JP18)
D02693  Devazepide (USAN/INN)
D02710  Tarazepide (INN)
D03442  Ceruletide (USAN/INN)
D03443  Ceruletide diethylamine (USAN)
D03605  Crofelemer (USAN)
D04028  Orlistat (JAN/USP/INN)
D04057  Esoxybutynin chloride (USAN)
D04970  Methacholine chloride (JAN/USP/INN)
D05183  Ulinastatin (JP18)
D05276  Pirenzepine hydrochloride hydrate (JP18)
D07820  Dicycloverine (INN)
D08325  Oxyphencyclimine (INN)
D08382  Piperidolate (INN)
D08389  Pirenzepine (INN)
D09208  Cetilistat (JAN/USAN/INN)
D10134  Lumacaftor (USAN/INN)
D10685  Lumacaftor and ivacaftor
D11042  Tezacaftor and ivacaftor
D11700  Elexacaftor, ivacaftor and tezacaftor
D11724  Galicaftor (USAN/INN)
D12140  Navocaftor (USAN/INN)
D12454  Icenticaftor (USAN/INN)
D12718  Vanzacaftor (USAN/INN)
D12719  Vanzacaftor calcium (USAN)
Other DBs
GO: 0030157
Homo sapiens (human) [GN:hsa]
1131  CHRM3; cholinergic receptor muscarinic 3 [KO:K04131]
885  CCK; cholecystokinin [KO:K05226]
886  CCKAR; cholecystokinin A receptor [KO:K04194]
2776  GNAQ; G protein subunit alpha q [KO:K04634]
23236  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:]
5330  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:]
5331  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:]
5332  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:]
5578  PRKCA; protein kinase C alpha [KO:K02677] [EC:]
5579  PRKCB; protein kinase C beta [KO:K19662] [EC:]
5582  PRKCG; protein kinase C gamma [KO:K19663] [EC:]
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; Rac family small GTPase 1 [KO:K04392]
278  AMY1C; amylase alpha 1C [KO:K01176] [EC:]
279  AMY2A; amylase alpha 2A [KO:K01176] [EC:]
276  AMY1A; amylase alpha 1A [KO:K01176] [EC:]
280  AMY2B; amylase alpha 2B [KO:K01176] [EC:]
277  AMY1B; amylase alpha 1B [KO:K01176] [EC:]
5646  PRSS3; serine protease 3 [KO:K01312] [EC:]
5645  PRSS2; serine protease 2 [KO:K01312] [EC:]
5644  PRSS1; serine protease 1 [KO:K01312] [EC:]
440387  CTRB2; chymotrypsinogen B2 [KO:K01310] [EC:]
1504  CTRB1; chymotrypsinogen B1 [KO:K01310] [EC:]
1506  CTRL; chymotrypsin like [KO:K09632] [EC:3.4.21.-]
63036  CELA2A; chymotrypsin like elastase 2A [KO:K01346] [EC:]
51032  CELA2B; chymotrypsin like elastase 2B [KO:K01346] [EC:]
10136  CELA3A; chymotrypsin like elastase 3A [KO:K01345] [EC:]
23436  CELA3B; chymotrypsin like elastase 3B [KO:K01345] [EC:]
1357  CPA1; carboxypeptidase A1 [KO:K08779] [EC:]
1358  CPA2; carboxypeptidase A2 [KO:K01298] [EC:]
1359  CPA3; carboxypeptidase A3 [KO:K08780] [EC:]
1360  CPB1; carboxypeptidase B1 [KO:K01291] [EC:]
1361  CPB2; carboxypeptidase B2 [KO:K01300] [EC:]
5406  PNLIP; pancreatic lipase [KO:K14073] [EC:]
5407  PNLIPRP1; pancreatic lipase related protein 1 [KO:K14074] [EC:]
5408  PNLIPRP2; pancreatic lipase related protein 2 (gene/pseudogene) [KO:K14075] [EC:]
1056  CEL; carboxyl ester lipase [KO:K12298] [EC:]
8399  PLA2G10; phospholipase A2 group X [KO:K01047] [EC:]
26279  PLA2G2D; phospholipase A2 group IID [KO:K01047] [EC:]
30814  PLA2G2E; phospholipase A2 group IIE [KO:K01047] [EC:]
50487  PLA2G3; phospholipase A2 group III [KO:K01047] [EC:]
64600  PLA2G2F; phospholipase A2 group IIF [KO:K01047] [EC:]
81579  PLA2G12A; phospholipase A2 group XIIA [KO:K01047] [EC:]
84647  PLA2G12B; phospholipase A2 group XIIB [KO:K01047] [EC:]
5319  PLA2G1B; phospholipase A2 group IB [KO:K01047] [EC:]
5322  PLA2G5; phospholipase A2 group V [KO:K01047] [EC:]
5320  PLA2G2A; phospholipase A2 group IIA [KO:K01047] [EC:]
391013  PLA2G2C; phospholipase A2 group IIC [KO:K01047] [EC:]
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 [KO:K04962]
952  CD38; CD38 molecule [KO:K01242] [EC:]
683  BST1; bone marrow stromal cell antigen 1 [KO:K18152] [EC:]
219931  TPCN2; two pore segment channel 2 [KO:K14077]
487  ATP2A1; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1 [KO:K05853] [EC:]
489  ATP2A3; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3 [KO:K05853] [EC:]
488  ATP2A2; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 [KO:K05853] [EC:]
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 member 2 [KO:K10951]
476  ATP1A1; ATPase Na+/K+ transporting subunit alpha 1 [KO:K01539] [EC:]
477  ATP1A2; ATPase Na+/K+ transporting subunit alpha 2 [KO:K01539] [EC:]
478  ATP1A3; ATPase Na+/K+ transporting subunit alpha 3 [KO:K01539] [EC:]
480  ATP1A4; ATPase Na+/K+ transporting subunit alpha 4 [KO:K01539] [EC:]
23439  ATP1B4; ATPase Na+/K+ transporting family member beta 4 [KO:K01540]
481  ATP1B1; ATPase Na+/K+ transporting subunit beta 1 [KO:K01540]
482  ATP1B2; ATPase Na+/K+ transporting subunit beta 2 [KO:K01540]
483  ATP1B3; ATPase Na+/K+ transporting subunit beta 3 [KO:K01540]
486  FXYD2; FXYD domain containing ion transport regulator 2 [KO:K01538]
3784  KCNQ1; potassium voltage-gated channel subfamily Q member 1 [KO:K04926]
3778  KCNMA1; potassium calcium-activated channel subfamily M alpha 1 [KO:K04936]
490  ATP2B1; ATPase plasma membrane Ca2+ transporting 1 [KO:K05850] [EC:]
492  ATP2B3; ATPase plasma membrane Ca2+ transporting 3 [KO:K05850] [EC:]
493  ATP2B4; ATPase plasma membrane Ca2+ transporting 4 [KO:K05850] [EC:]
491  ATP2B2; ATPase plasma membrane Ca2+ transporting 2 [KO:K05850] [EC:]
6548  SLC9A1; solute carrier family 9 member A1 [KO:K05742]
6522  SLC4A2; solute carrier family 4 member 2 [KO:K13855]
6343  SCT; secretin [KO:K05263]
6344  SCTR; secretin receptor [KO:K04588]
2778  GNAS; GNAS complex locus [KO:K04632]
107  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:]
108  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:]
109  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:]
196883  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:]
111  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:]
112  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:]
113  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:]
114  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:]
115  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:]
1080  CFTR; CF transmembrane conductance regulator [KO:K05031] [EC:]
1811  SLC26A3; solute carrier family 26 member 3 [KO:K14078]
8671  SLC4A4; solute carrier family 4 member 4 [KO:K13575]
760  CA2; carbonic anhydrase 2 [KO:K18245] [EC:]
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
Petersen OH, Tepikin AV
Polarized calcium signaling in exocrine gland cells.
Annu Rev Physiol 70:273-99 (2008)
Williams JA
Regulation of acinar cell function in the pancreas.
Curr Opin Gastroenterol 26:478-83 (2010)
Williams JA
Regulation of pancreatic acinar cell function.
Curr Opin Gastroenterol 22:498-504 (2006)
Bi Y, Williams JA
Receptor biology and signal transduction in pancreatic acinar cells.
Curr Opin Gastroenterol 20:427-34 (2004)
Yamasaki M, Masgrau R, Morgan AJ, Churchill GC, Patel S, Ashcroft SJ, Galione A
Organelle selection determines agonist-specific Ca2+ signals in pancreatic acinar and beta cells.
J Biol Chem 279:7234-40 (2004)
Kanno T
Ca2+ signaling in the pancreatic acinus.
Pancreas 16:273-6 (1998)
Heitzmann D, Warth R
Physiology and pathophysiology of potassium channels in gastrointestinal epithelia.
Physiol Rev 88:1119-82 (2008)
Konturek SJ, Zabielski R, Konturek JW, Czarnecki J
Neuroendocrinology of the pancreas; role of brain-gut axis in pancreatic secretion.
Eur J Pharmacol 481:1-14 (2003)
Chu JY, Yung WH, Chow BK
Secretin: a pleiotrophic hormone.
Ann N Y Acad Sci 1070:27-50 (2006)
Siu FK, Lam IP, Chu JY, Chow BK
Signaling mechanisms of secretin receptor.
Regul Pept 137:95-104 (2006)
Steward MC, Ishiguro H, Case RM
Mechanisms of bicarbonate secretion in the pancreatic duct.
Annu Rev Physiol 67:377-409 (2005)
Kim D, Steward MC
The role of CFTR in bicarbonate secretion by pancreatic duct and airway epithelia.
J Med Invest 56 Suppl:336-42 (2009)
Whitcomb DC, Lowe ME
Human pancreatic digestive enzymes.
Dig Dis Sci 52:1-17 (2007)
Cancela JM, Gerasimenko OV, Gerasimenko JV, Tepikin AV, Petersen OH
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.
EMBO J 19:2549-57 (2000)
Cancela JM, Churchill GC, Galione A
Coordination of agonist-induced Ca2+-signalling patterns by NAADP in pancreatic acinar cells.
Nature 398:74-6 (1999)
Parekh AB
Calcium signaling and acute pancreatitis: specific response to a promiscuous messenger.
Proc Natl Acad Sci U S A 97:12933-4 (2000)
Williams JA, Chen X, Sabbatini ME
Small G proteins as key regulators of pancreatic digestive enzyme secretion.
Am J Physiol Endocrinol Metab 296:E405-14 (2009)
hsa04020  Calcium signaling pathway
hsa04530  Tight junction
hsa04973  Carbohydrate digestion and absorption
hsa04974  Protein digestion and absorption
hsa04975  Fat digestion and absorption
hsa04977  Vitamin digestion and absorption
KO pathway

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