KEGG PATHWAY: rno04972

PATHWAY: rno04972

Entry

rno04972 Pathway

Name

Pancreatic secretion - Rattus norvegicus (rat)

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

rno04972

Pancreatic secretion

Other DBs

BSID:

169303

GO:

0030157

Organism

Rattus norvegicus (rat) [GN:rno]

Gene

24260	Chrm3; cholinergic receptor, muscarinic 3 [KO:K04131]
24889	Cckar; cholecystokinin A receptor [KO:K04194]
81666	Gnaq; guanine nucleotide binding protein (G protein), q polypeptide [KO:K04634]
24654	Plcb1; phospholipase C, beta 1 (phosphoinositide-specific) [KO:K05858] [EC:3.1.4.11]
29322	Plcb3; phospholipase C, beta 3 (phosphatidylinositol-specific) [KO:K05858] [EC:3.1.4.11]
85240	Plcb2; phospholipase C, beta 2 [KO:K05858] [EC:3.1.4.11]
25031	Plcb4; phospholipase C, beta 4 [KO:K05858] [EC:3.1.4.11]
24680	Prkca; protein kinase C, alpha [KO:K02677] [EC:2.7.11.13]
24681	Prkcg; protein kinase C, gamma [KO:K02677] [EC:2.7.11.13]
25023	Prkcb; protein kinase C, beta [KO:K02677] [EC:2.7.11.13]
140665	Rab3d; RAB3D, member RAS oncogene family [KO:K07884]
117103	Rab8a; RAB8A, member RAS oncogene family [KO:K07901]
81830	Rab11a; RAB11a, member RAS oncogene family [KO:K07904]
84590	Rab27b; RAB27B, member RAS oncogene family [KO:K07886]
295347	Rap1a; RAP1A, member of RAS oncogene family [KO:K04353]
171337	Rap1b; RAP1B, member of RAS oncogene family [KO:K07836]
117273	Rhoa; ras homolog family member A [KO:K04513]
297173	RSA-14-44; RSA-14-44 protein [KO:K04513]
363875	Rac1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
24691	Prss1; protease, serine, 1 (trypsin 1) [KO:K01312] [EC:3.4.21.4]
25052	Prss2; protease, serine, 2 [KO:K01312] [EC:3.4.21.4]
362347	Try4; trypsin 4 [KO:K01312] [EC:3.4.21.4]
286960	Try4; preprotrypsinogen IV [KO:K01312] [EC:3.4.21.4]
286911	Prss3; protease, serine, 3 [KO:K01312] [EC:3.4.21.4]
100912089	anionic trypsin-2-like; K01312 trypsin [EC:3.4.21.4] [KO:K01312] [EC:3.4.21.4]
683849	similar to Anionic trypsin II precursor (Pretrypsinogen II); K01312 trypsin [EC:3.4.21.4] [KO:K01312] [EC:3.4.21.4]
117184	Ctrl; chymotrypsin-like [KO:K09632] [EC:3.4.21.-]
24332	Cela2a; chymotrypsin-like elastase family, member 2A [KO:K01346] [EC:3.4.21.71]
298567	Cela3b; chymotrypsin-like elastase family, member 3B [KO:K01345] [EC:3.4.21.70]
24269	Cpa1; carboxypeptidase A1 (pancreatic) [KO:K08779] [EC:3.4.17.1]
296959	Cpa2; carboxypeptidase A2 (pancreatic) [KO:K01298] [EC:3.4.17.15]
54242	Cpa3; carboxypeptidase A3, mast cell [KO:K08780] [EC:3.4.17.1]
24271	Cpb1; carboxypeptidase B1 (tissue) [KO:K01291] [EC:3.4.17.2]
113936	Cpb2; carboxypeptidase B2 (plasma) [KO:K01300] [EC:3.4.17.20]
25702	Pnlip; pancreatic lipase [KO:K14073] [EC:3.1.1.3]
84028	Pnliprp1; pancreatic lipase-related protein 1 [KO:K14074] [EC:3.1.1.3]
117554	Pnliprp2; pancreatic lipase-related protein 2 [KO:K14075] [EC:3.1.1.3]
24254	Cel; carboxyl ester lipase [KO:K12298] [EC:3.1.1.3 3.1.1.13]
29354	Pla2g5; phospholipase A2, group V [KO:K01047] [EC:3.1.1.4]
29359	Pla2g10; phospholipase A2, group X [KO:K01047] [EC:3.1.1.4]
29387	Pla2g2c; phospholipase A2, group IIC [KO:K01047] [EC:3.1.1.4]
29526	Pla2g1b; phospholipase A2, group IB, pancreas [KO:K01047] [EC:3.1.1.4]
29692	Pla2g2a; phospholipase A2, group IIA (platelets, synovial fluid) [KO:K01047] [EC:3.1.1.4]
362039	Pla2g12a; phospholipase A2, group XIIA [KO:K01047] [EC:3.1.1.4]
289733	Pla2g3; phospholipase A2, group III [KO:K01047] [EC:3.1.1.4]
367415	Pla2g12b; phospholipase A2, group XIIB [KO:K01047] [EC:3.1.1.4]
298579	Pla2g2d; phospholipase A2, group IID [KO:K01047] [EC:3.1.1.4]
690388	Pla2g2f; phospholipase A2, group IIF [KO:K01047] [EC:3.1.1.4]
25262	Itpr1; inositol 1,4,5-trisphosphate receptor, type 1 [KO:K04958]
81678	Itpr2; inositol 1,4,5-trisphosphate receptor, type 2 [KO:K04959]
25679	Itpr3; inositol 1,4,5-trisphosphate receptor, type 3 [KO:K04960]
689560	Ryr2; ryanodine receptor 2, cardiac [KO:K04962]
81506	Bst1; bone marrow stromal cell antigen 1 [KO:K01242] [EC:3.2.2.5]
25668	Cd38; CD38 molecule [KO:K01242] [EC:3.2.2.5]
309139	Tpcn2; two pore segment channel 2 [KO:K14077]
116601	Atp2a1; ATPase, Ca++ transporting, cardiac muscle, fast twitch 1 [KO:K05853] [EC:3.6.3.8]
29693	Atp2a2; ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 [KO:K05853] [EC:3.6.3.8]
25391	Atp2a3; ATPase, Ca++ transporting, ubiquitous [KO:K05853] [EC:3.6.3.8]
308015	Clca1; chloride channel accessory 1 [KO:K05027]
308016	Clca5; chloride channel calcium activated 5 [KO:K05028]
362053	Clca4; chloride channel accessory 4 [KO:K05030]
362052	Clca2; chloride channel calcium activated 2 [KO:K05030]
499721	Clca4l; chloride channel calcium activated 4-like [KO:K05030]
89821	Trpc1; transient receptor potential cation channel, subfamily C, member 1 [KO:K04964]
83629	Slc12a2; solute carrier family 12 (sodium/potassium/chloride transporters), member 2 [KO:K10951]
24211	Atp1a1; ATPase, Na+/K+ transporting, alpha 1 polypeptide [KO:K01539] [EC:3.6.3.9]
24212	Atp1a2; ATPase, Na+/K+ transporting, alpha 2 polypeptide [KO:K01539] [EC:3.6.3.9]
24213	Atp1a3; ATPase, Na+/K+ transporting, alpha 3 polypeptide [KO:K01539] [EC:3.6.3.9]
29132	Atp1a4; ATPase, Na+/K+ transporting, alpha 4 polypeptide [KO:K01539] [EC:3.6.3.9]
84396	Atp1b4; ATPase, (Na+)/K+ transporting, beta 4 polypeptide [KO:K01540]
25650	Atp1b1; ATPase, Na+/K+ transporting, beta 1 polypeptide [KO:K01540]
24214	Atp1b2; ATPase, Na+/K+ transporting, beta 2 polypeptide [KO:K01540]
25390	Atp1b3; ATPase, Na+/K+ transporting, beta 3 polypeptide [KO:K01540]
29639	Fxyd2; FXYD domain-containing ion transport regulator 2 [KO:K01538]
84020	Kcnq1; potassium voltage-gated channel, KQT-like subfamily, member 1 [KO:K04926]
83731	Kcnma1; potassium large conductance calcium-activated channel, subfamily M, alpha member 1 [KO:K04936]
29600	Atp2b4; ATPase, Ca++ transporting, plasma membrane 4 [KO:K05850] [EC:3.6.3.8]
29599	Atp2b3; ATPase, Ca++ transporting, plasma membrane 3 [KO:K05850] [EC:3.6.3.8]
24215	Atp2b2; ATPase, Ca++ transporting, plasma membrane 2 [KO:K05850] [EC:3.6.3.8]
29598	Atp2b1; ATPase, Ca++ transporting, plasma membrane 1 [KO:K05850] [EC:3.6.3.8]
24782	Slc9a1; solute carrier family 9, subfamily A (NHE1, cation proton antiporter 1), member 1 [KO:K05742]
24780	Slc4a2; solute carrier family 4 (anion exchanger), member 2 [KO:K13855]
81779	Sctr; secretin receptor [KO:K04588]
24896	Gnas; GNAS complex locus [KO:K04632]
305509	Adcy1; adenylate cyclase 1 (brain) [KO:K08041] [EC:4.6.1.1]
81636	Adcy2; adenylate cyclase 2 (brain) [KO:K08042] [EC:4.6.1.1]
64508	Adcy3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
54223	Adcy4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
64532	Adcy5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
25289	Adcy6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
84420	Adcy7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
29241	Adcy8; adenylate cyclase 8 (brain) [KO:K08048] [EC:4.6.1.1]
302950	Adcy9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
24255	Cftr; cystic fibrosis transmembrane conductance regulator [KO:K05031] [EC:3.6.3.49]
114629	Slc26a3; solute carrier family 26, member 3 [KO:K14078]
84484	Slc4a4; solute carrier family 4, sodium bicarbonate cotransporter, member 4 [KO:K13575]
24291	Ctrb1; chymotrypsinogen B1 [KO:K01310] [EC:3.4.21.1]
54231	Ca2; carbonic anhydrase 2 [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

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Pathway (1)   
   BioSystems (1)   
Genome (1)   
   KEGG GENOME (1)   
Gene (100)   
   KEGG GENES (100)   
All databases (102)   

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