KEGG   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
rno04972

Other DBs
GO: 0030157
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
102554637  [KO:K01312] [EC:3.4.21.4]
103689940  [KO:K01176] [EC:3.2.1.1]
103690254  Try5; trypsin-4 isoform X1 [KO:K01312] [EC:3.4.21.4]
113936  Cpb2; carboxypeptidase B2 precursor [KO:K01300] [EC:3.4.17.20]
114629  Slc26a3; chloride anion exchanger [KO:K14078]
116601  Atp2a1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 [KO:K05853] [EC:7.2.2.10]
117103  Rab8a; ras-related protein Rab-8A [KO:K07901]
117184  Ctrl; chymotrypsin-like protease CTRL-1 precursor [KO:K09632] [EC:3.4.21.-]
117273  Rhoa; transforming protein RhoA [KO:K04513]
117554  Pnliprp2; pancreatic lipase-related protein 2 precursor [KO:K14075] [EC:3.1.1.3]
120100609  [KO:K01176] [EC:3.2.1.1]
120100610  [KO:K01176] [EC:3.2.1.1]
140665  Rab3d; GTP-binding protein Rab-3D [KO:K07884]
171337  Rap1b; ras-related protein Rap-1b precursor [KO:K07836]
24203  Amy1; alpha-amylase 1 precursor [KO:K01176] [EC:3.2.1.1]
24211  Atp1a1; sodium/potassium-transporting ATPase subunit alpha-1 precursor [KO:K01539] [EC:7.2.2.13]
24212  Atp1a2; sodium/potassium-transporting ATPase subunit alpha-2 precursor [KO:K01539] [EC:7.2.2.13]
24213  Atp1a3; sodium/potassium-transporting ATPase subunit alpha-3 [KO:K01539] [EC:7.2.2.13]
24214  Atp1b2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
24215  Atp2b2; plasma membrane calcium-transporting ATPase 2 [KO:K05850] [EC:7.2.2.10]
24254  Cel; bile salt-activated lipase precursor [KO:K12298] [EC:3.1.1.3 3.1.1.13]
24255  Cftr; cystic fibrosis transmembrane conductance regulator [KO:K05031] [EC:5.6.1.6]
24260  Chrm3; muscarinic acetylcholine receptor M3 [KO:K04131]
24269  Cpa1; carboxypeptidase A1 preproprotein [KO:K08779] [EC:3.4.17.1]
24271  Cpb1; carboxypeptidase B precursor [KO:K01291] [EC:3.4.17.2]
24291  Ctrb1; chymotrypsinogen B precursor [KO:K01310] [EC:3.4.21.1]
24332  Cela2a; chymotrypsin-like elastase family member 2A precursor [KO:K01346] [EC:3.4.21.71]
24654  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
24680  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
24681  Prkcg; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
24691  Prss1; serine protease 1 precursor [KO:K01312] [EC:3.4.21.4]
24769  Sct; secretin precursor [KO:K05263]
24780  Slc4a2; anion exchange protein 2 [KO:K13855]
24782  Slc9a1; sodium/hydrogen exchanger 1 [KO:K05742]
24889  Cckar; cholecystokinin receptor type A [KO:K04194]
24896  Gnas; SCG6 (secretogranin VI) isoform SCG6 precursor [KO:K04632]
25023  Prkcb; protein kinase C beta type isoform 2 [KO:K19662] [EC:2.7.11.13]
25031  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
25052  Prss2; anionic trypsin-2 precursor [KO:K01312] [EC:3.4.21.4]
25262  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform 3 [KO:K04958]
25289  Adcy6; adenylate cyclase type 6 isoform 2 [KO:K08046] [EC:4.6.1.1]
25298  Cck; cholecystokinin preproprotein [KO:K05226]
25390  Atp1b3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
25391  Atp2a3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 [KO:K05853] [EC:7.2.2.10]
25650  Atp1b1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
25668  Cd38; ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 [KO:K01242] [EC:3.2.2.6 2.4.99.20]
25679  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
25702  Pnlip; pancreatic triacylglycerol lipase precursor [KO:K14073] [EC:3.1.1.3]
286911  Prss3b; cationic trypsin-3 precursor [KO:K01312] [EC:3.4.21.4]
286960  1810009J06Rikl; trypsin-4 precursor [KO:K01312] [EC:3.4.21.4]
289733  Pla2g3; group 3 secretory phospholipase A2 precursor [KO:K01047] [EC:3.1.1.4]
29132  Atp1a4; sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
29241  Adcy8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
29322  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
29354  Pla2g5; phospholipase A2 group V precursor [KO:K01047] [EC:3.1.1.4]
29359  Pla2g10; group 10 secretory phospholipase A2 precursor [KO:K01047] [EC:3.1.1.4]
29387  Pla2g2c; group IIC secretory phospholipase A2 precursor [KO:K01047] [EC:3.1.1.4]
29526  Pla2g1b; phospholipase A2 precursor [KO:K01047] [EC:3.1.1.4]
295347  Rap1a; ras-related protein Rap-1A [KO:K04353]
29598  Atp2b1; plasma membrane calcium-transporting ATPase 1 isoform 3 [KO:K05850] [EC:7.2.2.10]
29599  Atp2b3; plasma membrane calcium-transporting ATPase 3 [KO:K05850] [EC:7.2.2.10]
29600  Atp2b4; plasma membrane calcium-transporting ATPase 4 [KO:K05850] [EC:7.2.2.10]
29639  Fxyd2; sodium/potassium-transporting ATPase subunit gamma isoform a [KO:K01538]
29692  Pla2g2a; phospholipase A2, membrane associated precursor [KO:K01047] [EC:3.1.1.4]
29693  Atp2a2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform b [KO:K05853] [EC:7.2.2.10]
296959  Cpa2; carboxypeptidase A2 precursor [KO:K01298] [EC:3.4.17.15]
297173  RSA-14-44; ras homolog gene family, member A [KO:K04513]
298567  Cela3b; chymotrypsin-like elastase family member 3B precursor [KO:K01345] [EC:3.4.21.70]
298579  Pla2g2d; group IID secretory phospholipase A2 precursor [KO:K01047] [EC:3.1.1.4]
298581  Pla2g2e; group IIE secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
302950  Adcy9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
305509  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
308015  Clca1; calcium-activated chloride channel regulator 1 precursor [KO:K05027]
308016  Clca2; calcium-activated chloride channel regulator 2 [KO:K05028]
309139  Tpcn2; two pore channel protein 2 [KO:K14077]
312273  Prss3bl1; trypsin V-A precursor [KO:K01312] [EC:3.4.21.4]
362039  Pla2g12a; group XIIA secretory phospholipase A2 precursor [KO:K01047] [EC:3.1.1.4]
362052  Clca5; chloride channel accessory 5 precursor [KO:K05030]
362053  Clca4; calcium-activated chloride channel regulator 4 precursor [KO:K05030]
362347  Prss3; serine protease 3 precursor [KO:K01312] [EC:3.4.21.4]
363875  Rac1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
367415  Pla2g12b; group XIIB secretory phospholipase A2-like protein isoform X2 [KO:K01047] [EC:3.1.1.4]
408247  Try10; trypsin 10 precursor [KO:K01312] [EC:3.4.21.4]
497039  Amy2a3; pancreatic alpha-amylase precursor [KO:K01176] [EC:3.2.1.1]
499721  Clca4l; chloride channel calcium activated 4-like precursor [KO:K05030]
54223  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
54231  Car2; carbonic anhydrase 2 [KO:K18245] [EC:4.2.1.1]
54242  Cpa3; mast cell carboxypeptidase A precursor [KO:K08780] [EC:3.4.17.1]
64508  Adcy3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
64532  Adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
683849  Prss2l1; anionic trypsin-2 [KO:K01312] [EC:3.4.21.4]
689560  Ryr2; ryanodine receptor 2 isoform 1 [KO:K04962]
690388  Pla2g2f; group IIF secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
81506  Bst1; ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2 precursor [KO:K18152] [EC:3.2.2.6 2.4.99.20]
81636  Adcy2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
81666  Gnaq; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
81678  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
81779  Sctr; secretin receptor precursor [KO:K04588]
81830  Rab11a; ras-related protein Rab-11A [KO:K07904]
83629  Slc12a2; solute carrier family 12 member 2 [KO:K10951]
83731  Kcnma1; calcium-activated potassium channel subunit alpha-1 isoform 1 [KO:K04936]
84020  Kcnq1; potassium voltage-gated channel subfamily KQT member 1 [KO:K04926]
84028  Pnliprp1; inactive pancreatic lipase-related protein 1 precursor [KO:K14074] [EC:3.1.1.3]
84396  Atp1b4; protein ATP1B4 [KO:K01540]
84420  Adcy7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
84484  Slc4a4; electrogenic sodium bicarbonate cotransporter 1 [KO:K13575]
84590  Rab27b; ras-related protein Rab-27B [KO:K07886]
85240  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
89821  Trpc1; short transient receptor potential channel 1 isoform 2 [KO:K04964]
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
Reference
PMID:17850212
  Authors
Petersen OH, Tepikin AV
  Title
Polarized calcium signaling in exocrine gland cells.
  Journal
Annu Rev Physiol 70:273-99 (2008)
DOI:10.1146/annurev.physiol.70.113006.100618
Reference
PMID:20625287
  Authors
Williams JA
  Title
Regulation of acinar cell function in the pancreas.
  Journal
Curr Opin Gastroenterol 26:478-83 (2010)
DOI:10.1097/MOG.0b013e32833d11c6
Reference
PMID:16891880
  Authors
Williams JA
  Title
Regulation of pancreatic acinar cell function.
  Journal
Curr Opin Gastroenterol 22:498-504 (2006)
DOI:10.1097/01.mog.0000239863.96833.c0
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)
DOI:10.1097/00001574-200409000-00002
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)
DOI:10.1074/jbc.M311088200
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)
DOI:10.1152/physrev.00020.2007
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)
DOI:10.1016/j.ejphar.2003.08.042
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)
DOI:10.1196/annals.1317.013
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)
DOI:10.1016/j.regpep.2006.02.011
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)
DOI:10.1146/annurev.physiol.67.031103.153247
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)
DOI:10.2152/jmi.56.336
Reference
PMID:17205399
  Authors
Whitcomb DC, Lowe ME
  Title
Human pancreatic digestive enzymes.
  Journal
Dig Dis Sci 52:1-17 (2007)
DOI:10.1007/s10620-006-9589-z
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)
DOI:10.1093/emboj/19.11.2549
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)
DOI:10.1038/18032
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)
DOI:10.1073/pnas.97.24.12933
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)
DOI:10.1152/ajpendo.90874.2008
Related
pathway
rno04020  Calcium signaling pathway
rno04530  Tight junction
rno04973  Carbohydrate digestion and absorption
rno04974  Protein digestion and absorption
rno04975  Fat digestion and absorption
rno04977  Vitamin digestion and absorption
KO pathway
ko04972   

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