KEGG   PATHWAY: hsa04971
Entry
hsa04971                    Pathway                                
Name
Gastric acid secretion - Homo sapiens (human)
Description
Gastric acid is a key factor in normal upper gastrointestinal functions, including protein digestion and calcium and iron absorption, as well as providing some protection against bacterial infections. The principal stimulants of acid secretion at the level of the parietal cell are histamine (paracrine), gastrin (hormonal), and acetycholine (ACh; neurocrine). Stimulation of acid secretion typically involves an initial elevation of intracellular calcium and cAMP, followed by activation of protein kinase cascades, which trigger the translocation of the proton pump, H+,K+-ATPase, from cytoplasmic tubulovesicles to the apical plasma membrane and thereby H+ secretion into the stomach lumen.
Class
Organismal Systems; Digestive system
Pathway map
hsa04971  Gastric acid secretion
hsa04971

Drug
D00113  Atropine (USP)
D00147  Hyoscyamine (USP)
D00295  Cimetidine (JP19/USP/INN)
D00318  Famotidine (JP19/USP/INN)
D00355  Lansoprazole (JP19/USP/INN)
D00397  Tropicamide (JP19/USP/INN)
D00422  Ranitidine (USAN/INN)
D00440  Nizatidine (JP19/USP/INN)
D00442  Octreotide (USAN/INN)
D00455  Omeprazole (JP19/USP/INN)
D00481  Propantheline bromide (JP19/USP/INN)
D00540  Glycopyrrolate (USP)
D00673  Ranitidine hydrochloride (JP19/USP)
D00715  Methscopolamine bromide (USP)
D00716  Clidinium bromide (USP/INN)
D00717  Dicyclomine hydrochloride (JAN/USP)
D00719  Hyoscyamine sulfate (USP)
D00720  Mepenzolate bromide (JP19/INN)
D00721  Methanthelinium bromide (INN)
D00724  Rabeprazole sodium (JP19/USP)
D00999  Acetylcholine chloride (JP19/USP/INN)
D01000  Bethanechol chloride (JP19/USP)
D01003  Hexocyclium metilsulfate (INN)
D01005  Isopropamide iodide (JAN/USP/INN)
D01006  Oxyphencyclimine hydrochloride (JAN)
D01131  Lafutidine (JP19/INN)
D01165  Piperidolate hydrochloride (JAN)
D01187  Betazole hydrochloride (JAN)
D01207  Omeprazole sodium (USAN)
D01297  Pirenzepine hydrochloride (USAN)
D01315  Methylbenactyzium bromide (JP19/INN)
D01359  Etomidoline (JAN/INN)
D01451  Scopolamine butylbromide (JP19)
D01467  Roxatidine acetate hydrochloride (JP19/USAN)
D01491  Butropium bromide (JP19/INN)
D01521  Pipethanate hydrochloride (JAN)
D01538  Valethamate bromide (JAN)
D01600  Diphenylpiperidinomethyldioxolan iodide (JAN)
D01631  Pentagastrin (JAN/USAN/INN)
D01648  Hyoscyamine methylbromide (JAN)
D01815  Oxapium iodide (JP19/INN)
D01818  Proglumide (JP19/USAN/INN)
D01861  Pibutidine hydrochloride (JAN)
D01875  Tiquizium bromide (JAN/INN)
D01920  Tenatoprazole (JAN/INN)
D01955  Aclatonium napadisilate (JAN)
D01976  N-Methylscopolamine methylsulfate (JAN)
D01984  Esomeprazole magnesium (USP)
D01987  Pipethanate ethobromide (JAN)
D02069  Atropine sulfate (JP19/USP)
D02108  Indium In 111 pentetreotide (USP)
D02250  Octreotide acetate (JAN)
D02535  Timepidium bromide hydrate (JP19)
D02593  Pantoprazole sodium (USP)
D03503  Cimetidine hydrochloride (USP)
D03605  Crofelemer (USAN)
D03889  Donetidine (USAN)
D03979  Elucaine (USAN)
D04056  Esomeprazole sodium (USAN)
D04057  Esoxybutynin chloride (USAN)
D04098  Etintidine hydrochloride (USAN)
D04445  Histamine phosphate (USP)
D04479  Hyoscyamine hydrobromide (USP)
D04517  Impromidine hydrochloride (USAN)
D04666  Lanreotide acetate (JAN/USAN)
D04680  Lavoltidine succinate (USAN)
D04794  Lupitidine hydrochloride (USAN)
D04970  Methacholine chloride (JAN/USP/INN)
D05004  Metiamide (USAN/INN)
D05012  Metoquizine (USAN/INN)
D05230  Octreotide pamoate (USAN)
D05259  Omeprazole magnesium (USP)
D05261  Omeprazole sodium injection (JAN)
D05276  Pirenzepine hydrochloride hydrate (JP19)
D05353  Pantoprazole (USAN/INN)
D05699  Ranitidine bismuth citrate (USAN)
D05722  Revaprazan hydrochloride (USAN)
D05812  Seglitide acetate (USAN)
D05900  Timoprazole (INN)
D05901  Picoprazole (INN)
D05906  Leminoprazole (INN)
D05939  Sufotidine (USAN/INN)
D06157  Tiotidine (USAN/INN)
D06192  Toquizine (USAN)
D06281  Vapreotide (USAN/INN)
D06355  Zaltidine hydrochloride (USAN)
D06495  Octreotide acetate (USP)
D06878  Diphemanil metilsulfate (INN)
D07072  Niperotidine (INN)
D07431  Somatostatin (INN)
D07820  Dicycloverine (INN)
D07917  Esomeprazole (INN)
D08325  Oxyphencyclimine (INN)
D08382  Piperidolate (INN)
D08384  Pipethanate (INN)
D08389  Pirenzepine (USAN/INN)
D08463  Rabeprazole (INN)
D08494  Roxatidine (INN)
D08495  Roxatidine acetate (BAN)
D08595  Tiemonium methylsulfate
D08903  Dexlansoprazole (INN/USAN)
D09339  Esomeprazole potassium (USAN)
D09837  Penaprazole sodium hydrate (JAN)
D09916  Ivacaftor (USAN/INN)
D09988  Vapreotide acetate (USAN)
D10120  Esomeprazole strontium (USAN)
D10134  Lumacaftor (USAN/INN)
D10147  Pasireotide (USAN)
D10466  Vonoprazan fumarate (JAN/USAN)
D10497  Pasireotide diaspartate
D10566  Pasireotide pamoate (JAN)
D10685  Lumacaftor and ivacaftor
D11033  Lutetium (177Lu) oxodotreotide (INN)
D11042  Tezacaftor and ivacaftor
D11114  Esomeprazole magnesium dihydrate
D11192  Veldoreotide (USAN/INN)
D11204  Octreotide hydrochloride (USAN)
D11700  Elexacaftor, ivacaftor and tezacaftor
D11724  Galicaftor (USAN/INN)
D11784  Vonoprazan (USAN/INN)
D11882  Copper Cu 64 dotatate
D12140  Navocaftor (USAN/INN)
D12246  Tegoprazan (INN)
D12431  Lutetium Lu177 edotreotide (USAN)
D12454  Icenticaftor (USAN/INN)
D12718  Vanzacaftor (USAN/INN)
D12719  Vanzacaftor calcium (USAN)
D12816  Dexlansoprazole sesquihydrate
D12907  Actinium Ac 225 dotatate (USAN)
D13012  Fexuprazan (INN)
D13013  Ilaprazole (INN)
D13024  Vanzacaftor, tezacaftor and deutivacaftor
D13197  Linaprazan glurate (USAN/INN)
D13198  Linaprazan glurate hydrochloride (USAN)
D13240  Zastaprazan (INN)
Other DBs
GO: 0001696
Organism
Homo sapiens (human) [GN:hsa]
Gene
107  ADCY1; adenylate cyclase type 1 isoform 1 [KO:K08041] [EC:4.6.1.1]
108  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
1080  CFTR; cystic fibrosis transmembrane conductance regulator [KO:K05031] [EC:5.6.1.6]
109  ADCY3; adenylate cyclase type 3 isoform 2 [KO:K08043] [EC:4.6.1.1]
111  ADCY5; adenylate cyclase type 5 isoform 1 [KO:K08045] [EC:4.6.1.1]
112  ADCY6; adenylate cyclase type 6 isoform 1 [KO:K08046] [EC:4.6.1.1]
113  ADCY7; adenylate cyclase type 7 isoform 1 [KO:K08047] [EC:4.6.1.1]
1131  CHRM3; muscarinic acetylcholine receptor M3 [KO:K04131]
114  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
115  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
115111  SLC26A7; anion exchange transporter isoform a [KO:K13962]
163688  CALML6; calmodulin-like protein 6 isoform 1 [KO:K02183]
196883  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
23236  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform a [KO:K05858] [EC:3.1.4.11]
23439  ATP1B4; protein ATP1B4 isoform A [KO:K01540]
2520  GAST; gastrin preproprotein [KO:K13768]
2770  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform 1 [KO:K04630]
2771  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform 1 [KO:K04630]
2773  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
2776  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
2778  GNAS; protein GNAS isoform XLas [KO:K04632]
3274  HRH2; histamine H2 receptor isoform 1 [KO:K04150]
340156  MYLK4; myosin light chain kinase family member 4 isoform 1 [KO:K00907] [EC:2.7.11.18]
3708  ITPR1; inositol 1,4,5-trisphosphate-gated calcium channel ITPR1 isoform 4 [KO:K04958]
3709  ITPR2; inositol 1,4,5-trisphosphate-gated calcium channel ITPR2 isoform 1 [KO:K04959]
3710  ITPR3; inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 [KO:K04960]
3758  KCNJ1; ATP-sensitive inward rectifier potassium channel 1 isoform a [KO:K04995]
3759  KCNJ2; inward rectifier potassium channel 2 [KO:K04996]
3766  KCNJ10; ATP-sensitive inward rectifier potassium channel 10 [KO:K05003]
3772  KCNJ15; ATP-sensitive inward rectifier potassium channel 15 [KO:K05008]
3773  KCNJ16; inward rectifier potassium channel 16 isoform b [KO:K05009]
3776  KCNK2; potassium channel subfamily K member 2 isoform c [KO:K04913]
3784  KCNQ1; potassium voltage-gated channel subfamily KQT member 1 isoform 1 [KO:K04926]
389015  SLC9A4; sodium/hydrogen exchanger 4 precursor [KO:K13961]
4638  MYLK; myosin light chain kinase, smooth muscle isoform 1 [KO:K00907] [EC:2.7.11.18]
476  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 isoform a [KO:K01539] [EC:7.2.2.13]
477  ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 precursor [KO:K01539] [EC:7.2.2.13]
478  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 isoform 1 [KO:K01539] [EC:7.2.2.13]
480  ATP1A4; sodium/potassium-transporting ATPase subunit alpha-4 isoform 1 [KO:K01539] [EC:7.2.2.13]
481  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
482  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 isoform 1 [KO:K01540]
483  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
495  ATP4A; potassium-transporting ATPase alpha chain 1 [KO:K01542] [EC:7.2.2.19]
496  ATP4B; potassium-transporting ATPase subunit beta [KO:K01543] [EC:7.2.2.19]
51806  CALML5; calmodulin-like protein 5 [KO:K02183]
5330  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform 1 [KO:K05858] [EC:3.1.4.11]
5331  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform 1 [KO:K05858] [EC:3.1.4.11]
5332  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform b [KO:K05858] [EC:3.1.4.11]
54207  KCNK10; potassium channel subfamily K member 10 isoform 1 precursor [KO:K04920]
5566  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform Calpha1 [KO:K04345] [EC:2.7.11.11]
5567  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform 2 [KO:K04345] [EC:2.7.11.11]
5568  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
5578  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
5579  PRKCB; protein kinase C beta type isoform 1 [KO:K19662] [EC:2.7.11.13]
5582  PRKCG; protein kinase C gamma type isoform 2 [KO:K19663] [EC:2.7.11.13]
60  ACTB; actin, cytoplasmic 1 [KO:K05692]
6522  SLC4A2; anion exchange protein 2 isoform 1 [KO:K13855]
6548  SLC9A1; sodium/hydrogen exchanger 1 [KO:K05742]
6750  SST; somatostatin preproprotein [KO:K05237]
6752  SSTR2; somatostatin receptor type 2 [KO:K04218]
71  ACTG1; actin, cytoplasmic 2 [KO:K05692]
7430  EZR; ezrin [KO:K08007]
760  CA2; carbonic anhydrase 2 isoform 1 [KO:K18245] [EC:4.2.1.1]
801  CALM1; calmodulin-1 isoform 2 [KO:K02183]
805  CALM2; calmodulin-2 isoform 2 [KO:K02183]
808  CALM3; calmodulin-3 isoform 1 [KO:K02183]
810  CALML3; calmodulin-like protein 3 [KO:K02183]
815  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform 2 [KO:K04515] [EC:2.7.11.17]
816  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform 1 [KO:K04515] [EC:2.7.11.17]
817  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform 3 [KO:K04515] [EC:2.7.11.17]
818  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform 7 [KO:K04515] [EC:2.7.11.17]
85366  MYLK2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
887  CCKBR; gastrin/cholecystokinin type B receptor isoform 1 [KO:K04195]
91807  MYLK3; myosin light chain kinase 3 isoform 1 [KO:K00907] [EC:2.7.11.18]
91860  CALML4; calmodulin-like protein 4 isoform 1 [KO:K02183]
9992  KCNE2; potassium voltage-gated channel subfamily E member 2 [KO:K04896]
Compound
C00001  H2O
C00011  CO2
C00076  Calcium cation
C00080  H+
C00165  Diacylglycerol
C00238  Potassium cation
C00288  HCO3-
C00388  Histamine
C00575  3',5'-Cyclic AMP
C00698  Cl-
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
C01353  Carbonic acid
C01996  Acetylcholine
Reference
PMID:18474247
  Authors
Schubert ML, Peura DA
  Title
Control of gastric acid secretion in health and disease.
  Journal
Gastroenterology 134:1842-60 (2008)
DOI:10.1053/j.gastro.2008.05.021
Reference
PMID:9307437
  Authors
Urushidani T, Forte JG
  Title
Signal transduction and activation of acid secretion in the parietal cell.
  Journal
J Membr Biol 159:99-111 (1997)
DOI:10.1007/s002329900274
Reference
PMID:12500969
  Authors
Yao X, Forte JG
  Title
Cell biology of acid secretion by the parietal cell.
  Journal
Annu Rev Physiol 65:103-31 (2003)
DOI:10.1146/annurev.physiol.65.072302.114200
Reference
PMID:17928547
  Authors
Heitzmann D, Warth R
  Title
No potassium, no acid: K+ channels and gastric acid secretion.
  Journal
Physiology (Bethesda) 22:335-41 (2007)
DOI:10.1152/physiol.00016.2007
Reference
PMID:19889964
  Authors
Kopic S, Murek M, Geibel JP
  Title
Revisiting the parietal cell.
  Journal
Am J Physiol Cell Physiol 298:C1-C10 (2010)
DOI:10.1152/ajpcell.00478.2009
Reference
PMID:15703676
  Authors
Schubert ML
  Title
Gastric secretion.
  Journal
Curr Opin Gastroenterol 20:519-25 (2004)
DOI:10.1097/00001574-200411000-00003
Reference
PMID:16391411
  Authors
Konturek SJ, Konturek PC, Brzozowski T, Konturek JW, Pawlik WW
  Title
From nerves and hormones to bacteria in the stomach; Nobel prize for achievements in gastrology during last century.
  Journal
J Physiol Pharmacol 56:507-30 (2005)
Reference
PMID:20148676
  Authors
Forte JG, Zhu L
  Title
Apical recycling of the gastric parietal cell H,K-ATPase.
  Journal
Annu Rev Physiol 72:273-96 (2010)
DOI:10.1146/annurev-physiol-021909-135744
Reference
PMID:18061403
  Authors
Szaszak M, Christian F, Rosenthal W, Klussmann E
  Title
Compartmentalized cAMP signalling in regulated exocytic processes in non-neuronal cells.
  Journal
Cell Signal 20:590-601 (2008)
DOI:10.1016/j.cellsig.2007.10.020
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:15579540
  Authors
Heitzmann D, Grahammer F, von Hahn T, Schmitt-Graff A, Romeo E, Nitschke R, Gerlach U, Lang HJ, Verrey F, Barhanin J, Warth R
  Title
Heteromeric KCNE2/KCNQ1 potassium channels in the luminal membrane of gastric parietal cells.
  Journal
J Physiol 561:547-57 (2004)
DOI:10.1113/jphysiol.2004.075168
Reference
PMID:20331540
  Authors
Seidler U, Song P, Xiao F, Riederer B, Bachmann O, Chen M
  Title
Recent advances in the molecular and functional characterization of acid/base and electrolyte transporters in the basolateral membranes of gastric and duodenal epithelial cells.
  Journal
Acta Physiol (Oxf) 201:3-20 (2011)
DOI:10.1111/j.1748-1716.2010.02107.x
Related
pathway
hsa04020  Calcium signaling pathway
hsa04530  Tight junction
hsa04974  Protein digestion and absorption
KO pathway
ko04971   

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