KEGG PATHWAY: hsa04972

PATHWAY: hsa04972

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

Pathway map

hsa04972

Pancreatic secretion

Disease

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:

169306

GO:

0030157

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:3.2.2.5]
683	BST1; bone marrow stromal cell antigen 1 [KO:K01242] [EC:3.2.2.5]
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 transporters), 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 (erythrocyte membrane protein band 3-like 1) [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, 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

PMID:17850212

Authors

Petersen OH, Tepikin AV

Title

Polarized calcium signaling in exocrine gland cells.

Journal

Annu Rev Physiol 70:273-99 (2008)

Reference

PMID:20625287

Authors

Williams JA

Title

Regulation of acinar cell function in the pancreas.

Journal

Curr Opin Gastroenterol 26:478-83 (2010)

Reference

PMID:16891880

Authors

Williams JA

Title

Regulation of pancreatic acinar cell function.

Journal

Curr Opin Gastroenterol 22:498-504 (2006)

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)

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)

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)

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)

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)

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)

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)

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)

Reference

PMID:17205399

Authors

Whitcomb DC, Lowe ME

Title

Human pancreatic digestive enzymes.

Journal

Dig Dis Sci 52:1-17 (2007)

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)

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)

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)

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)

KO pathway

ko04972

All links

Ontology (3)   
   KEGG BRITE (3)   
Pathway (1)   
   BioSystems (1)   
Disease (1)   
   KEGG DISEASE (1)   
Drug (42)   
   KEGG DRUG (42)   
Genome (1)   
   KEGG GENOME (1)   
Gene (98)   
   KEGG GENES (98)   
All databases (146)   

Download RDF

DBGET integrated database retrieval system