KEGG   PATHWAY: hsa04970Help
Entry
hsa04970                    Pathway                                

Name
Salivary secretion - Homo sapiens (human)
Description
Saliva has manifold functions in maintaining the integrity of the oral tissues, in protecting teeth from caries, in the tasting and ingestion of food, in speech and in the tolerance of tenures, for example. Salivary secretion occurs in response to stimulation by neurotransmitters released from autonomic nerve endings. There are two secretory pathways: protein exocytosis and fluid secretion. Sympathetic stimulation leads to the activation of adenylate cyclase and accumulation of intracellular cAMP. The elevation of cAMP causes the secretion of proteins such as amylase and mucin. In contrast, parasympathetic stimulation activates phospholipase C and causes the elevation of intracellular Ca2+, which leads to fluid secretion; that is, water and ion transport. Ca2+ also induces amylase secretion, but the amount is smaller than that induced by cAMP.
Class
Organismal Systems; Digestive system
BRITE hierarchy
Pathway map
Salivary secretion
hsa04970

All organismsOrtholog table
Disease
H00845  
Familial amyloidosis
Drug
D00095  
Epinephrine (USP/INN)
D00124  
Ephedrine (USP)
D00147  
Hyoscyamine (USP)
D00232  
Anisotropine methylbromide (USAN)
D00235  
Atenolol (JP17/USP/INN)
D00397  
Tropicamide (JP17/USP/INN)
D00483  
Propranolol hydrochloride (JP17/USP)
D00485  
Pseudoephedrine hydrochloride (USP)
D00513  
Pindolol (JP17/USP/INN)
D00524  
Carbachol (JAN/USP/INN)
D00597  
Acebutolol hydrochloride (JP17/USP)
D00601  
Metoprolol tartrate (JP17/USP)
D00602  
Penbutolol sulfate (JP17/USP)
D00607  
Guanadrel sulfate (USP)
D00610  
Terazosin hydrochloride (USAN)
D00635  
Metoprolol succinate (USP)
D00644  
Esmolol hydrochloride (JAN/USAN)
D00646  
Tolterodine (USAN/INN)
D00661  
Cevimeline hydrochloride (USAN)
D00715  
Methscopolamine bromide (USP)
D00717  
Dicyclomine hydrochloride (JAN/USP)
D00719  
Hyoscyamine sulfate (USP)
D00743  
Naphazoline hydrochloride (JP17/USP)
D00756  
Tetrahydrozoline nitrate (JAN)
D00996  
Epinephrine hydrochloride (JAN)
D00999  
Acetylcholine chloride (JP17/USP/INN)
D01000  
Bethanechol chloride (JP17/USP)
D01002  
Cyclopentolate hydrochloride (JP17/USP)
D01004  
Homatropine hydrobromide (JP17/USP)
D01017  
Dipivefrin hydrochloride (JAN/USP)
D01021  
Naphazoline nitrate (JP17)
D01022  
Oxymetazoline hydrochloride (JAN/USP)
D01023  
Tetrahydrozoline hydrochloride (JAN/USP)
D01103  
Trospium chloride (JAN/USAN/INN)
D01148  
Tolterodine tartrate (JAN/USAN)
D01165  
Piperidolate hydrochloride (JAN)
D01182  
Alprenolol hydrochloride (JP17/USAN)
D01269  
Solifenacin succinate (JAN/USAN/INN)
D01307  
Midodrine hydrochloride (JAN/USAN)
D01315  
Methylbenactyzium bromide (JP17/INN)
D01323  
Azosemide (JAN/USAN/INN)
D01359  
Etomidoline (JAN/INN)
D01386  
Ephedrine hydrochloride (JP17/USP)
D01444  
Bunitrolol hydrochloride (JAN)
D01454  
Bupranolol hydrochloride (JP17)
D01463  
Diponium bromide (JAN/INN)
D01471  
Esatenolol (JAN/INN)
D01491  
Butropium bromide (JP17/INN)
D01504  
Bufetolol hydrochloride (JP17)
D01512  
Befunolol hydrochloride (JAN)
D01521  
Pipethanate hydrochloride (JAN)
D01538  
Valethamate bromide (JAN)
D01600  
Diphenylpiperidinomethyldioxolan iodide (JAN)
D01648  
Hyoscyamine methylbromide (JAN)
D01674  
Naftopidil (JP17/INN)
D01692  
Alfuzosin hydrochloride (JAN/USAN)
D01699  
Darifenacin hydrobromide (JAN/USAN)
D01741  
Celiprolol hydrochloride (JAN/USAN)
D01794  
Bopindolol malonate (JAN)
D01806  
Oxprenolol hydrochloride (JP17/USP)
D01815  
Oxapium iodide (JP17/INN)
D01847  
Landiolol hydrochloride (JAN)
D01875  
Tiquizium bromide (JAN/INN)
D01887  
Bunazosin hydrochloride (JP17)
D01952  
L-Methylephedrine hydrochloride (JAN)
D01955  
Aclatonium napadisilate (JAN)
D01987  
Pipethanate ethobromide (JAN)
D02070  
Homatropine methylbromide (USP)
D02081  
Metipranolol hydrochloride
D02109  
dl-Methylephedrine hydrochloride (JP17)
D02200  
Pilocarpine hydrochloride (JP17/USP)
D02338  
Acebutolol (USAN/INN)
D02349  
Dipivefrin (USAN)
D02358  
Metoprolol (USAN/INN)
D02374  
Metipranolol (USAN/INN)
D02389  
Primidolol (USAN/INN)
D02417  
Flutropium bromide (JAN)
D02535  
Timepidium bromide hydrate (JP17)
D02614  
Denopamine (JAN/INN)
D02834  
Alprenoxime hydrochloride (USAN)
D02876  
Alvameline maleate (USAN)
D03011  
Atropine oxide hydrochloride (USAN)
D03170  
Bucindolol hydrochloride (USAN)
D03177  
Bunolol hydrochloride (USAN)
D03195  
Butopamine (USAN/INN)
D03449  
Cetamolol hydrochloride (USAN)
D03490  
Cicloprolol hydrochloride (USAN)
D03502  
Cimaterol (USAN/INN)
D03648  
Dapiprazole hydrochloride (USAN)
D03654  
Darifenacin (USAN/INN)
D03729  
Dexpropranolol hydrochloride (USAN)
D03759  
Diacetolol hydrochloride (USAN)
D03880  
Dobutamine lactobionate (USAN)
D03881  
Dobutamine tartrate (USP)
D04018  
Ephedrine sulfate (USP)
D04057  
Esoxybutynin chloride (USAN)
D04116  
Eucatropine hydrochloride (USP XXXII)
D04184  
Fiduxosin hydrochloride (USAN)
D04190  
Flestolol sulfate (USAN)
D04479  
Hyoscyamine hydrobromide (USP)
D04888  
Medroxalol (USAN/INN)
D04889  
Medroxalol hydrochloride (USAN)
D04970  
Methacholine chloride (JAN/USAN/INN)
D05011  
Metoprolol fumarate (USP)
D05035  
Milameline hydrochloride (USAN)
D05127  
Nebivolol (USAN/INN)
D05345  
Pamatolol sulfate (USAN)
D05648  
Pseudoephedrine polistirex (USAN)
D05649  
Pseudoephedrine sulfate (USP)
D06273  
Imidafenacin (JAN/INN)
D06622  
Nebivolol hydrochloride (USAN)
D06878  
Diphemanil metilsulfate (INN)
D07124  
Alfuzosin (INN)
D07156  
Alprenolol (INN)
D07182  
Tertatolol (INN)
D07183  
Cloranolol (INN)
D07349  
Choline alfoscerate (INN)
D07477  
Atropine oxide (INN)
D07537  
Bopindolol (INN)
D07550  
Bunazosin (INN)
D07590  
Bupranolol (INN)
D07660  
Celiprolol (INN)
D07667  
Cevimeline (INN)
D07759  
Cyclopentolate (INN)
D07820  
Dicycloverine (INN)
D07916  
Esmolol (INN)
D08074  
Penbutolol (INN)
D08206  
Methylephedrine (BAN)
D08209  
Metixene (INN)
D08220  
Midodrine (INN)
D08253  
Naphazoline (INN)
D08318  
Oxprenolol (INN)
D08322  
Oxymetazoline (INN)
D08382  
Piperidolate (INN)
D08384  
Pipethanate (INN)
D08443  
Propranolol (INN)
D08449  
Pseudoephedrine (INN)
D08522  
Solifenacin (INN)
D08569  
Terazosin (INN)
D08572  
Tertatolol hydrochloride
D08578  
Tetryzoline (INN)
D08595  
Tiemonium methylsulfate
D09842  
dl-Methylephedrine saccharinate (JAN)
Other DBs
BSID: 
GO: 
Organism
Homo sapiens (human) [GN:hsa]
Gene
153  
ADRB1; adrenoceptor beta 1 [KO:K04141]
154  
ADRB2; adrenoceptor beta 2 [KO:K04142]
155  
ADRB3; adrenoceptor beta 3 [KO:K04143]
2778  
GNAS; GNAS complex locus [KO:K04632]
107  
ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
108  
ADCY2; adenylate cyclase 2 [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 [KO:K08048] [EC:4.6.1.1]
115  
ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
5566  
PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
5567  
PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
5568  
PRKACG; protein kinase cAMP-activated catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
6844  
VAMP2; vesicle associated membrane protein 2 [KO:K13504]
148  
ADRA1A; adrenoceptor alpha 1A [KO:K04135]
147  
ADRA1B; adrenoceptor alpha 1B [KO:K04136]
146  
ADRA1D; adrenoceptor alpha 1D [KO:K04137]
1131  
CHRM3; cholinergic receptor muscarinic 3 [KO:K04131]
2776  
GNAQ; G protein subunit alpha q [KO:K04634]
23236  
PLCB1; phospholipase C beta 1 [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 [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:K19662] [EC:2.7.11.13]
5582  
PRKCG; protein kinase C gamma [KO:K19663] [EC:2.7.11.13]
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]
6263  
RYR3; ryanodine receptor 3 [KO:K04963]
810  
CALML3; calmodulin like 3 [KO:K02183]
805  
CALM2; calmodulin 2 [KO:K02183]
808  
CALM3; calmodulin 3 [KO:K02183]
801  
CALM1; calmodulin 1 [KO:K02183]
163688  
CALML6; calmodulin like 6 [KO:K02183]
51806  
CALML5; calmodulin like 5 [KO:K02183]
91860  
CALML4; calmodulin like 4 [KO:K02183]
4842  
NOS1; nitric oxide synthase 1 [KO:K13240] [EC:1.14.13.39]
2977  
GUCY1A2; guanylate cyclase 1 soluble subunit alpha 2 [KO:K12318] [EC:4.6.1.2]
2982  
GUCY1A1; guanylate cyclase 1 soluble subunit alpha 1 [KO:K12318] [EC:4.6.1.2]
2983  
GUCY1B1; guanylate cyclase 1 soluble subunit beta 1 [KO:K12319] [EC:4.6.1.2]
5592  
PRKG1; protein kinase, cGMP-dependent, type I [KO:K07376] [EC:2.7.11.12]
5593  
PRKG2; protein kinase, cGMP-dependent, type II [KO:K19477] [EC:2.7.11.12]
952  
CD38; CD38 molecule [KO:K01242] [EC:2.4.99.20 3.2.2.6]
683  
BST1; bone marrow stromal cell antigen 1 [KO:K18152] [EC:2.4.99.20 3.2.2.6]
54831  
BEST2; bestrophin 2 [KO:K13879]
362  
AQP5; aquaporin 5 [KO:K09867]
476  
ATP1A1; ATPase Na+/K+ transporting subunit alpha 1 [KO:K01539] [EC:3.6.3.9]
477  
ATP1A2; ATPase Na+/K+ transporting subunit alpha 2 [KO:K01539] [EC:3.6.3.9]
478  
ATP1A3; ATPase Na+/K+ transporting subunit alpha 3 [KO:K01539] [EC:3.6.3.9]
480  
ATP1A4; ATPase Na+/K+ transporting subunit alpha 4 [KO:K01539] [EC:3.6.3.9]
23439  
ATP1B4; ATPase Na+/K+ transporting family member beta 4 [KO:K01540]
481  
ATP1B1; ATPase Na+/K+ transporting subunit beta 1 [KO:K01540]
482  
ATP1B2; ATPase Na+/K+ transporting subunit beta 2 [KO:K01540]
483  
ATP1B3; ATPase Na+/K+ transporting subunit beta 3 [KO:K01540]
486  
FXYD2; FXYD domain containing ion transport regulator 2 [KO:K01538]
490  
ATP2B1; ATPase plasma membrane Ca2+ transporting 1 [KO:K05850] [EC:3.6.3.8]
492  
ATP2B3; ATPase plasma membrane Ca2+ transporting 3 [KO:K05850] [EC:3.6.3.8]
493  
ATP2B4; ATPase plasma membrane Ca2+ transporting 4 [KO:K05850] [EC:3.6.3.8]
491  
ATP2B2; ATPase plasma membrane Ca2+ transporting 2 [KO:K05850] [EC:3.6.3.8]
6558  
SLC12A2; solute carrier family 12 member 2 [KO:K10951]
3783  
KCNN4; potassium calcium-activated channel subfamily N member 4 [KO:K04945]
3778  
KCNMA1; potassium calcium-activated channel subfamily M alpha 1 [KO:K04936]
6522  
SLC4A2; solute carrier family 4 member 2 [KO:K13855]
6548  
SLC9A1; solute carrier family 9 member A1 [KO:K05742]
55503  
TRPV6; transient receptor potential cation channel subfamily V member 6 [KO:K04975]
727897  
MUC5B; mucin 5B, oligomeric mucus/gel-forming [KO:K13908]
4589  
MUC7; mucin 7, secreted [KO:K13909]
5555  
PRH2; proline rich protein HaeIII subfamily 2 [KO:K13910]
5554  
PRH1; proline rich protein HaeIII subfamily 1 [KO:K13910]
5542  
PRB1; proline rich protein BstNI subfamily 1 [KO:K13911]
653247  
PRB2; proline rich protein BstNI subfamily 2 [KO:K13911]
1755  
DMBT1; deleted in malignant brain tumors 1 [KO:K13912]
1469  
CST1; cystatin SN [KO:K13897]
1470  
CST2; cystatin SA [KO:K13898]
1471  
CST3; cystatin C [KO:K13899]
1472  
CST4; cystatin S [KO:K13900]
1473  
CST5; cystatin D [KO:K13901]
3346  
HTN1; histatin 1 [KO:K13913]
3347  
HTN3; histatin 3 [KO:K13913]
6779  
STATH; statherin [KO:K13914]
4069  
LYZ; lysozyme [KO:K13915] [EC:3.2.1.17]
4025  
LPO; lactoperoxidase [KO:K12550] [EC:1.11.1.7]
820  
CAMP; cathelicidin antimicrobial peptide [KO:K13916]
276  
AMY1A; amylase, alpha 1A (salivary) [KO:K01176] [EC:3.2.1.1]
277  
AMY1B; amylase, alpha 1B (salivary) [KO:K01176] [EC:3.2.1.1]
278  
AMY1C; amylase, alpha 1C (salivary) [KO:K01176] [EC:3.2.1.1]
Compound
C00001  
H2O
C00011  
CO2
C00076  
Calcium cation
C00080  
H+
C00165  
Diacylglycerol
C00238  
Potassium cation
C00288  
HCO3-
C00533  
Nitric oxide
C00547  
L-Noradrenaline
C00575  
3',5'-Cyclic AMP
C00698  
Cl-
C00942  
3',5'-Cyclic GMP
C01245  
D-myo-Inositol 1,4,5-trisphosphate
C01330  
Sodium cation
C01353  
Carbonic acid
C01996  
Acetylcholine
C13050  
Cyclic ADP-ribose
Reference
  Authors
Ishikawa Y, Cho G, Yuan Z, Skowronski MT, Pan Y, Ishida H
  Title
Water channels and zymogen granules in salivary glands.
  Journal
J Pharmacol Sci 100:495-512 (2006)
DOI:10.1254/jphs.CRJ06007X
Reference
  Authors
Ishikawa Y, Cho G, Yuan Z, Inoue N, Nakae Y
  Title
Aquaporin-5 water channel in lipid rafts of rat parotid glands.
  Journal
Biochim Biophys Acta 1758:1053-60 (2006)
DOI:10.1016/j.bbamem.2006.03.026
Reference
  Authors
Ambudkar IS
  Title
Regulation of calcium in salivary gland secretion.
  Journal
Crit Rev Oral Biol Med 11:4-25 (2000)
DOI:10.1177/10454411000110010301
Reference
  Authors
Ishikawa Y, Ishida H
  Title
Aquaporin water channel in salivary glands.
  Journal
Jpn J Pharmacol 83:95-101 (2000)
DOI:10.1254/jjp.83.95
Reference
PMID:8105741
  Authors
Baum BJ
  Title
Principles of saliva secretion.
  Journal
Ann N Y Acad Sci 694:17-23 (1993)
DOI:10.1111/j.1749-6632.1993.tb18338.x
Reference
PMID:9720759
  Authors
Fujita-Yoshigaki J
  Title
Divergence and convergence in regulated exocytosis: the characteristics of cAMP-dependent enzyme secretion of parotid salivary acinar cells.
  Journal
Cell Signal 10:371-5 (1998)
DOI:10.1016/S0898-6568(97)00178-2
Reference
  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
  Authors
Proctor GB, Carpenter GH
  Title
Regulation of salivary gland function by autonomic nerves.
  Journal
Auton Neurosci 133:3-18 (2007)
DOI:10.1016/j.autneu.2006.10.006
Reference
  Authors
Turner RJ, Sugiya H
  Title
Understanding salivary fluid and protein secretion.
  Journal
Oral Dis 8:3-11 (2002)
DOI:10.1034/j.1601-0825.2002.10815.x
Reference
  Authors
Van Nieuw Amerongen A, Bolscher JG, Veerman EC
  Title
Salivary proteins: protective and diagnostic value in cariology?
  Journal
Caries Res 38:247-53 (2004)
DOI:10.1159/000077762
Reference
  Authors
Nakamoto T, Srivastava A, Romanenko VG, Ovitt CE, Perez-Cornejo P, Arreola J, Begenisich T, Melvin JE
  Title
Functional and molecular characterization of the fluid secretion mechanism in human parotid acinar cells.
  Journal
Am J Physiol Regul Integr Comp Physiol 292:R2380-90 (2007)
DOI:10.1152/ajpregu.00591.2006
Reference
  Authors
Melvin JE, Yule D, Shuttleworth T, Begenisich T
  Title
Regulation of fluid and electrolyte secretion in salivary gland acinar cells.
  Journal
Annu Rev Physiol 67:445-69 (2005)
DOI:10.1146/annurev.physiol.67.041703.084745
Reference
  Authors
Catalan MA, Nakamoto T, Melvin JE
  Title
The salivary gland fluid secretion mechanism.
  Journal
J Med Invest 56 Suppl:192-6 (2009)
DOI:10.2152/jmi.56.192
KO pathway
 

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