KEGG   PATHWAY: hmh04972
Entry
hmh04972                    Pathway                                
Name
Pancreatic secretion - Hylobates moloch (silvery gibbon)
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
hmh04972  Pancreatic secretion
hmh04972

Other DBs
GO: 0030157
Organism
Hylobates moloch (silvery gibbon) [GN:hmh]
Gene
116456200  [KO:K01540]
116456838  CD38; ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 [KO:K01242] [EC:3.2.2.6 2.4.99.20]
116456971  BST1; ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2 [KO:K18152] [EC:3.2.2.6 2.4.99.20]
116457004  CCKAR; cholecystokinin receptor type A [KO:K04194]
116457100  ADCY2; LOW QUALITY PROTEIN: adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
116457249  ATP2B4; plasma membrane calcium-transporting ATPase 4 isoform X1 [KO:K05850] [EC:7.2.2.10]
116458043  CHRM3; muscarinic acetylcholine receptor M3 [KO:K04131]
116458053  RYR2; ryanodine receptor 2 isoform X6 [KO:K04962]
116458509  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X1 [KO:K05853] [EC:7.2.2.10]
116459014  PLA2G3; group 3 secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
116459050  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
116459267  [KO:K01047] [EC:3.1.1.4]
116459671  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
116459993  KCNMA1; calcium-activated potassium channel subunit alpha-1 isoform X1 [KO:K04936]
116461202  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
116461370  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X2 [KO:K05858] [EC:3.1.4.11]
116461629  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 isoform X1 [KO:K01540]
116461706  TRPC1; short transient receptor potential channel 1 isoform X1 [KO:K04964]
116461805  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
116462297  ADCY9; adenylate cyclase type 9 isoform X2 [KO:K08049] [EC:4.6.1.1]
116462689  PLA2G12A; group XIIA secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
116462880  SCTR; secretin receptor [KO:K04588]
116463273  [KO:K04632]
116463274  [KO:K04632]
116463360  [KO:K04632]
116463361  [KO:K04632]
116463683  [KO:K01047] [EC:3.1.1.4]
116463687  [KO:K01047] [EC:3.1.1.4]
116465001  [KO:K01346] [EC:3.4.21.71]
116465004  [KO:K01346] [EC:3.4.21.71]
116466582  SCT; secretin [KO:K05263]
116466681  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
116466736  ATP2B2; plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:7.2.2.10]
116466852  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
116467082  SLC4A4; electrogenic sodium bicarbonate cotransporter 1 isoform X1 [KO:K13575]
116467479  CPB2; carboxypeptidase B2 [KO:K01300] [EC:3.4.17.20]
116468527  RAB27B; ras-related protein Rab-27B isoform X1 [KO:K07886]
116468938  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
116469112  TPCN2; two pore channel protein 2 isoform X1 [KO:K14077]
116469141  KCNQ1; potassium voltage-gated channel subfamily KQT member 1 isoform X1 [KO:K04926]
116469214  ATP1A4; sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
116469215  ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
116469279  [KO:K04513]
116469557  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
116469612  RAP1A; ras-related protein Rap-1A [KO:K04353]
116469693  [KO:K01176] [EC:3.2.1.1]
116469816  [KO:K05030]
116469819  CLCA1; calcium-activated chloride channel regulator 1 [KO:K05027]
116469820  CLCA2; calcium-activated chloride channel regulator 2 isoform X1 [KO:K05028]
116470186  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X2 [KO:K05853] [EC:7.2.2.10]
116470816  [KO:K01310] [EC:3.4.21.1]
116470865  SLC12A2; solute carrier family 12 member 2 isoform X1 [KO:K10951]
116471147  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
116471246  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
116471403  CTRL; LOW QUALITY PROTEIN: chymotrypsin-like protease CTRL-1 [KO:K09632] [EC:3.4.21.-]
116472793  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
116473267  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
116473478  RHOA; transforming protein RhoA [KO:K04513]
116473615  CCK; cholecystokinin [KO:K05226]
116475178  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
116475807  CEL; bile salt-activated lipase [KO:K12298] [EC:3.1.1.3 3.1.1.13]
116476686  [KO:K05263]
116476994  FXYD2; sodium/potassium-transporting ATPase subunit gamma isoform X1 [KO:K01538]
116477947  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
116478472  [KO:K14075] [EC:3.1.1.3]
116478475  RAB3D; ras-related protein Rab-3D isoform X2 [KO:K07884]
116478481  [KO:K14074] [EC:3.1.1.3]
116478633  RAB8A; ras-related protein Rab-8A [KO:K07901]
116478979  RAP1B; ras-related protein Rap-1b [KO:K07836]
116479072  ATP2B1; plasma membrane calcium-transporting ATPase 1 isoform X1 [KO:K05850] [EC:7.2.2.10]
116479165  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
116479390  PLA2G1B; phospholipase A2 [KO:K01047] [EC:3.1.1.4]
116480241  CPA3; mast cell carboxypeptidase A [KO:K08780] [EC:3.4.17.1]
116480287  [KO:K04392]
116480405  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
116480604  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 isoform X1 [KO:K01539] [EC:7.2.2.13]
116481117  CPB1; carboxypeptidase B [KO:K01291] [EC:3.4.17.2]
116481969  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X6 [KO:K05858] [EC:3.1.4.11]
116481998  RAB11A; ras-related protein Rab-11A [KO:K07904]
116483124  [KO:K14073] [EC:3.1.1.3]
116483969  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
116484980  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
116809415  [KO:K01312] [EC:3.4.21.4]
116810870  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
116810950  CFTR; cystic fibrosis transmembrane conductance regulator [KO:K05031] [EC:5.6.1.6]
116811385  ATP1B4; protein ATP1B4 isoform X1 [KO:K01540]
116812065  [KO:K04632]
116812192  ATP2B3; plasma membrane calcium-transporting ATPase 3 isoform X1 [KO:K05850] [EC:7.2.2.10]
116812447  [KO:K01312] [EC:3.4.21.4]
116812469  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
116812648  PLA2G2F; group IIF secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
116813022  PLA2G2A; phospholipase A2, membrane associated [KO:K01047] [EC:3.1.1.4]
116813023  PLA2G5; phospholipase A2 group V isoform X2 [KO:K01047] [EC:3.1.1.4]
116813140  SLC9A1; sodium/hydrogen exchanger 1 [KO:K05742]
116813377  CA2; carbonic anhydrase 2 [KO:K18245] [EC:4.2.1.1]
116813595  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
116813793  [KO:K01345] [EC:3.4.21.70]
116813919  PLA2G2E; group IIE secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
116813921  PLA2G2D; group IID secretory phospholipase A2 isoform X1 [KO:K01047] [EC:3.1.1.4]
116813922  PLA2G2C; LOW QUALITY PROTEIN: putative inactive group IIC secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
116814236  SLC26A3; chloride anion exchanger [KO:K14078]
116814357  CPA2; LOW QUALITY PROTEIN: carboxypeptidase A2 [KO:K01298] [EC:3.4.17.15]
116814359  CPA1; carboxypeptidase A1 [KO:K08779] [EC:3.4.17.1]
116814446  [KO:K01312] [EC:3.4.21.4]
116814447  [KO:K01312] [EC:3.4.21.4]
116814537  SLC4A2; anion exchange protein 2 [KO:K13855]
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
hmh04020  Calcium signaling pathway
hmh04530  Tight junction
hmh04973  Carbohydrate digestion and absorption
hmh04974  Protein digestion and absorption
hmh04975  Fat digestion and absorption
hmh04977  Vitamin digestion and absorption
KO pathway
ko04972   

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