KEGG   PATHWAY: rno04976
Entry
rno04976                    Pathway                                
Name
Bile secretion - Rattus norvegicus (rat)
Description
Bile is a vital secretion, essential for digestion and absorption of fats and fat-soluble vitamins in the small intestine. Moreover, bile is an important route of elimination for excess cholesterol and many waste product, bilirubin, drugs and toxic compounds. Bile secretion depends on the function of membrane transport systems in hepatocytes and cholangiocytes and on the structural and functional integrity of the biliary tree. The hepatocytes generate the so-called primary bile in their canaliculi. Cholangiocytes modify the canalicular bile by secretory and reabsorptive processes as bile passes through the bile ducts. The main solutes in bile are bile acids, which stimulate bile secretion osmotically, as well as facilitate the intestinal absorption of dietary lipids by their detergent properties. Bile acids are also important signalling molecules. Through the activation of nuclear receptors, they regulate their own synthesis and transport rates.
Class
Organismal Systems; Digestive system
Pathway map
rno04976  Bile secretion
rno04976

Other DBs
GO: 0032782
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
25315  Ephx1; epoxide hydrolase 1 precursor [KO:K01253] [EC:3.3.2.9]
80900  Slco1a5; solute carrier organic anion transporter family member 1A5 [KO:K03460]
80899  Slco1a3; solute carrier organic anion transporter family member 1A3 [KO:K03460]
84608  Slco1a6; solute carrier organic anion transporter family member 1A6 [KO:K03460]
170698  Slco1a4; solute carrier organic anion transporter family member 1A4 [KO:K03460]
50572  Slco1a1; solute carrier organic anion transporter family member 1A1 [KO:K03460]
58978  Slco1b2; solute carrier organic anion transporter family member 1B2 isoform 1 [KO:K05043]
24777  Slc10a1; hepatic sodium/bile acid cotransporter [KO:K14341]
89776  Slc22a7; solute carrier family 22 member 7 [KO:K08204]
83500  Slc22a8; organic anion transporter 3 [KO:K08205]
24904  Slc22a1; solute carrier family 22 member 1 [KO:K08198]
25675  Hmgcr; 3-hydroxy-3-methylglutaryl-coenzyme A reductase [KO:K00021] [EC:1.1.1.34]
25073  Scarb1; scavenger receptor class B member 1 [KO:K13885]
300438  Ldlr; low-density lipoprotein receptor precursor [KO:K12473]
294930  Nceh1; neutral cholesterol ester hydrolase 1 [KO:K14349] [EC:3.1.1.-]
25428  Cyp7a1; cytochrome P450 7A1 [KO:K00489] [EC:1.14.14.23]
60351  Nr1h4; bile acid receptor [KO:K08537]
25271  Rxra; retinoic acid receptor RXR-alpha [KO:K08524]
117274  Nr0b2; nuclear receptor subfamily 0 group B member 2 [KO:K08563]
83808  Ugt2b35; UDP-glucuronosyltransferase 2B15 precursor [KO:K00699] [EC:2.4.1.17]
24862  Ugt2b; UDP-glucuronosyltransferase 2B2 precursor [KO:K00699] [EC:2.4.1.17]
63867  Ugt2a1; UDP-glucuronosyltransferase 2A1 precursor [KO:K00699] [EC:2.4.1.17]
574523  Ugt1a5; UDP-glucuronosyltransferase 1A5 precursor [KO:K00699] [EC:2.4.1.17]
301595  Ugt1a8; UDP-glucuronosyltransferase 1A8 precursor [KO:K00699] [EC:2.4.1.17]
24861  Ugt1a1; UDP-glucuronosyltransferase 1A1 precursor [KO:K00699] [EC:2.4.1.17]
113992  Ugt1a6; UDP-glucuronosyltransferase 1-6 precursor [KO:K00699] [EC:2.4.1.17]
289533  Ugt2a3; UDP-glucuronosyltransferase 2A3 precursor [KO:K00699] [EC:2.4.1.17]
266685  Ugt2b15; UDP-glucuronosyltransferase 2B17 precursor [KO:K00699] [EC:2.4.1.17]
29623  Ugt2b37; UDP-glucuronosyltransferase 2B37 precursor [KO:K00699] [EC:2.4.1.17]
286954  Ugt2b1; UDP-glucuronosyltransferase 2B1 precursor [KO:K00699] [EC:2.4.1.17]
396552  Ugt1a9; UDP glycosyltransferase 1 family, polypeptide A10 precursor [KO:K00699] [EC:2.4.1.17]
396551  Ugt1a3; UDP-glucuronosyltransferase 1A3 precursor [KO:K00699] [EC:2.4.1.17]
154516  Ugt1a7c; UDP-glucuronosyltransferase 1A7 precursor [KO:K00699] [EC:2.4.1.17]
396527  Ugt1a2; UDP-glucuronosyltransferase 1-2 precursor [KO:K00699] [EC:2.4.1.17]
305264  Ugt2b10; UDP-glucuronosyltransferase 2B10 precursor [KO:K00699] [EC:2.4.1.17]
286989  Ugt2b7; UDP-glucuronosyltransferase 2B7 precursor [KO:K00699] [EC:2.4.1.17]
501907  Ugt2b34l1; UDP-glucuronosyltransferase 2B31-like isoform X1 [KO:K00699] [EC:2.4.1.17]
134478834  UDP-glucuronosyltransferase 2B2 isoform X1 [KO:K00699] [EC:2.4.1.17]
24912  Sult2a1; sulfotransferase 2A1 [KO:K11822] [EC:2.8.2.14]
361510  Sult2a2; alcohol sulfotransferase [KO:K11822] [EC:2.8.2.14]
120099768  sulfotransferase 2A1 isoform X2 [KO:K11822] [EC:2.8.2.14]
134485278  alcohol sulfotransferase-like [KO:K11822] [EC:2.8.2.14]
79111  Slc27a5; long-chain fatty acid transport protein 5 [KO:K08748] [EC:6.2.1.7]
29725  Baat; bile acid-CoA:amino acid N-acyltransferase [KO:K00659] [EC:2.3.1.65 3.1.2.2]
681043  Acnat1; acyl-coenzyme A amino acid N-acyltransferase 2-like [KO:K00659] [EC:2.3.1.65 3.1.2.2]
313220  Acnat2; acyl-coenzyme A amino acid N-acyltransferase 2 [KO:K00659] [EC:2.3.1.65 3.1.2.2]
65054  Aqp9; aquaporin-9 [KO:K09877]
29172  Aqp8; aquaporin-8 [KO:K09869]
114628  Abcg5; ATP-binding cassette sub-family G member 5 [KO:K05683]
155192  Abcg8; ATP-binding cassette sub-family G member 8 [KO:K05684]
83569  Abcb11; bile salt export pump [KO:K05664]
25303  Abcc2; ATP-binding cassette sub-family C member 2 [KO:K05666]
312382  Abcg2; broad substrate specificity ATP-binding cassette transporter ABCG2 [KO:K05681]
54231  Car2; carbonic anhydrase 2 [KO:K18245] [EC:4.2.1.1]
24780  Slc4a2; anion exchange protein 2 [KO:K13855]
170913  Abcb1a; ATP binding cassette subfamily B member 1A [KO:K05658] [EC:7.6.2.2]
24646  Abcb1b; ATP-dependent translocase ABCB1 [KO:K05658] [EC:7.6.2.2]
24891  Abcb4; phosphatidylcholine translocator ABCB4 [KO:K05659] [EC:7.6.2.2]
24782  Slc9a1; sodium/hydrogen exchanger 1 [KO:K05742]
297386  Slc4a5; electrogenic sodium bicarbonate cotransporter 4 [KO:K13857]
140668  Abcc3; ATP-binding cassette sub-family C member 3 [KO:K05667]
170924  Abcc4; ATP-binding cassette subfamily C member 4 [KO:K05673]
303879  Slc51a; organic solute transporter subunit alpha [KO:K14360]
300790  Slc51b; organic solute transporter subunit beta [KO:K14361]
54262  Kcnn2; small conductance calcium-activated potassium channel protein 2 isoform 2 [KO:K04943]
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]
29132  Atp1a4; sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
84396  Atp1b4; protein ATP1B4 [KO:K01540]
25650  Atp1b1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
24214  Atp1b2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
25390  Atp1b3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
29639  Fxyd2; sodium/potassium-transporting ATPase subunit gamma isoform a [KO:K01538]
24769  Sct; secretin precursor [KO:K05263]
81779  Sctr; secretin receptor precursor [KO:K04588]
24896  Gnas; SCG6 (secretogranin VI) isoform SCG6 precursor [KO:K04632]
305509  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
81636  Adcy2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
64508  Adcy3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
54223  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
64532  Adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
25289  Adcy6; adenylate cyclase type 6 isoform 2 [KO:K08046] [EC:4.6.1.1]
84420  Adcy7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
29241  Adcy8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
302950  Adcy9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
25636  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
293508  Prkacb; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
24255  Cftr; cystic fibrosis transmembrane conductance regulator [KO:K05031] [EC:5.6.1.6]
84484  Slc4a4; electrogenic sodium bicarbonate cotransporter 1 [KO:K13575]
25293  Aqp4; aquaporin-4 isoform M1 [KO:K09866]
25240  Aqp1; aquaporin-1 [KO:K09864]
29500  Slc10a2; ileal sodium/bile acid cotransporter [KO:K14342]
25552  Slc5a1; sodium/glucose cotransporter 1 [KO:K14158]
365549  Slc5a1l1; uncharacterized protein LOC365549 [KO:K14158]
24784  Slc9a3; sodium/hydrogen exchanger 3 precursor [KO:K12040]
24778  Slc2a1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
Compound
C00001  H2O
C00011  CO2
C00024  Acetyl-CoA
C00026  2-Oxoglutarate
C00031  D-Glucose
C00051  Glutathione
C00080  H+
C00114  Choline
C00187  Cholesterol
C00238  Potassium cation
C00288  HCO3-
C00315  Spermidine
C00318  L-Carnitine
C00366  Urate
C00486  Bilirubin
C00504  Folate
C00575  3',5'-Cyclic AMP
C00584  Prostaglandin E2
C00639  Prostaglandin F2alpha
C00695  Cholic acid
C00698  Cl-
C00735  Cortisol
C00750  Spermine
C00780  Serotonin
C00805  Salicylate
C00865  Phospholipid
C00942  3',5'-Cyclic GMP
C01330  Sodium cation
C01353  Carbonic acid
C01405  Aspirin
C01443  Ouabain
C01576  Etoposide
C01829  Thyroxine
C01844  Pravastatin
C01921  Glycocholate
C01937  Methotrexate
C01996  Acetylcholine
C02165  Leukotriene B4
C02166  Leukotriene C4
C02380  6-Mercaptopurine
C02465  Triiodothyronine
C02528  Chenodeoxycholate
C02530  Cholesterol ester
C02538  Estrone 3-sulfate
C02918  1-Methylnicotinamide
C03033  beta-D-Glucuronoside
C03642  Taurolithocholate sulfate
C03758  Dopamine
C03990  Lithocholic acid
C04483  Deoxycholic acid
C04555  Dehydroepiandrosterone sulfate
C05122  Taurocholate
C05371  Microcystin LR
C05465  Taurochenodeoxycholate
C05466  Glycochenodeoxycholate
C05503  Estradiol-17beta 3-glucuronide
C05551  Penicillin G
C05963  Thromboxane B2
C06526  Quinine
C06570  Tetracycline
C06688  Rifampicin
C06804  Acetaminophen
C06810  Aciclovir
C06880  Cefazolin
C06890  Ceftizoxime
C06956  Digoxin
C06999  Fexofenadine
C07014  Fluvastatin
C07051  Indinavir
C07065  Lamivudine
C07151  Metformin
C07184  Valacyclovir
C07185  Valproic acid
C07201  Vinblastine
C07207  Zalcitabine
C07210  Zidovudine
C07240  Ritonavir
C07394  Paclitaxel
C07512  Tetraethylammonium
C07649  5-FU
C07660  Levofloxacin
C07966  Cerivastatin
C08357  Estradiol-17beta 3-sulfate
C08439  Phalloidin
C09955  Ochratoxin A
C11158  Topotecan
C11231  Docetaxel anhydrous
C11245  Glucuronosyletoposide
C11277  Adefovir
C11310  1-Methyl-4-phenylpyridinium
C11363  Sulfobromophthalein
C11587  BQ 123
C11754  Cephaloridine
C12560  Saquinavir mesylate
C16114  Cholecystokinin-8
C16578  Morphine-6-glucuronide
C16643  Morphine-3-glucuronide
D00125  Etoposide (JP18/USP/INN)
D00140  Erythromycin (JP18/USP/INN)
D00142  Methotrexate (JP18/USP/INN)
D00184  Cyclosporine (USP)
D00186  Ciprofloxacin (JP18/USP/INN)
D00201  Tetracycline (JAN/USP/INN)
D00214  Dactinomycin (USP)
D00224  Allopurinol (JP18/USP/INN)
D00240  Aztreonam (JP18/USP/INN)
D00247  Bumetanide (JP18/USP/INN)
D00295  Cimetidine (JP18/USP/INN)
D00298  Digoxin (JP18/USP)
D00318  Famotidine (JP18/USP/INN)
D00331  Furosemide (JP18/USP/INN)
D00333  Ganciclovir (JAN/USP/INN)
D00340  Hydrochlorothiazide (JP18/USP/INN)
D00353  Lamivudine (JAN/USP/INN)
D00359  Lovastatin (USP/INN)
D00400  Valsartan (JP18/USP/INN)
D00422  Ranitidine (USAN/INN)
D00427  Ritonavir (JAN/USP/INN)
D00429  Saquinavir (JAN/USP/INN)
D00439  Nitrofurantoin (JAN/USP/INN)
D00453  Ofloxacin (JP18/USP/INN)
D00456  Ondansetron (JAN/USP/INN)
D00491  Paclitaxel (JAN/USP/INN)
D00512  Phenytoin (JP18/USP/INN)
D00521  Terfenadine (JAN/USAN/INN)
D00570  Colchicine (JP18/USP)
D00590  Sparfloxacin (JAN/USAN/INN)
D00767  Vecuronium bromide (JAN/USP/INN)
D00804  Ivermectin (JAN/USP/INN)
D01061  Irinotecan hydrochloride (USP)
D01264  Daunorubicin hydrochloride (JP18/USP)
D01275  Doxorubicin hydrochloride (JP18/USP)
D01421  Aminohippurate sodium (USP)
D01745  Domperidone (JP18/USAN/INN)
D01862  Pitavastatin calcium (JAN)
D02115  Methotrexate sodium
D02166  Mitoxantrone hydrochloride (JAN/USP)
D02214  Epirubicin hydrochloride (JP18/USP)
D02216  Ciprofloxacin hydrochloride (USP)
D02356  Verapamil (USAN/INN)
D03130  Bisantrene hydrochloride (USAN)
D03833  Indinavir (USAN)
D03899  Doxorubicin (USAN/INN)
D04931  Mercaptopurine (INN)
D05246  Olmesartan (USAN/INN)
D06050  Technetium Tc 99m tetrofosmin (USP)
D06074  Tenofovir (USAN)
D07448  Amitriptyline (INN)
D07538  Bosentan (INN)
D07626  Caspofungin (INN)
D07661  Cerivastatin (INN)
D07776  Daunorubicin (INN)
D07845  Diltiazem (INN)
D07866  Docetaxel (JAN/INN)
D07901  Epirubicin (INN)
D07907  Erlotinib (INN)
D07958  Fexofenadine (INN)
D07986  Folinic acid (BAN)
D07987  Folinic acid calcium salt pentahydrate
D08066  Imatinib (INN)
D08086  Irinotecan (INN)
D08108  Lapatinib (INN)
D08144  Loperamide (INN)
D08146  Losartan (INN)
D08224  Mitoxantrone (INN)
D08259  Nelfinavir (INN)
D08291  Ofloxacin hydrochloride
D08306  Oseltamivir (INN)
D08411  Prazosin (INN)
D08458  Quinidine (BAN)
D08492  Rosuvastatin (INN)
D08618  Topotecan (BAN)
D08675  Vinblastine (INN)
D08679  Vincristine (INN)
Reference
PMID:11826283
  Authors
Meier PJ, Stieger B
  Title
Bile salt transporters.
  Journal
Annu Rev Physiol 64:635-61 (2002)
DOI:10.1146/annurev.physiol.64.082201.100300
Reference
PMID:10728790
  Authors
Kullak-Ublick GA, Beuers U, Paumgartner G
  Title
Hepatobiliary transport.
  Journal
J Hepatol 32:3-18 (2000)
DOI:10.1016/S0168-8278(00)80411-0
Reference
PMID:18668439
  Authors
Kosters A, Karpen SJ
  Title
Bile acid transporters in health and disease.
  Journal
Xenobiotica 38:1043-71 (2008)
DOI:10.1080/00498250802040584
Reference
PMID:14999673
  Authors
Anwer MS
  Title
Cellular regulation of hepatic bile acid transport in health and cholestasis.
  Journal
Hepatology 39:581-90 (2004)
DOI:10.1002/hep.20090
Reference
PMID:17404808
  Authors
Alrefai WA, Gill RK
  Title
Bile acid transporters: structure, function, regulation and pathophysiological implications.
  Journal
Pharm Res 24:1803-23 (2007)
DOI:10.1007/s11095-007-9289-1
Reference
PMID:12663868
  Authors
Trauner M, Boyer JL
  Title
Bile salt transporters: molecular characterization, function, and regulation.
  Journal
Physiol Rev 83:633-71 (2003)
DOI:10.1152/physrev.00027.2002
Reference
PMID:20103563
  Authors
Klaassen CD, Aleksunes LM
  Title
Xenobiotic, bile acid, and cholesterol transporters: function and regulation.
  Journal
Pharmacol Rev 62:1-96 (2010)
DOI:10.1124/pr.109.002014
Reference
PMID:15758646
  Authors
Trauner M, Wagner M, Fickert P, Zollner G
  Title
Molecular regulation of hepatobiliary transport systems: clinical implications for understanding and treating cholestasis.
  Journal
J Clin Gastroenterol 39:S111-24 (2005)
DOI:10.1097/01.mcg.0000155551.37266.26
Reference
PMID:14659471
  Authors
Arrese M, Trauner M
  Title
Molecular aspects of bile formation and cholestasis.
  Journal
Trends Mol Med 9:558-64 (2003)
DOI:10.1016/j.molmed.2003.10.002
Reference
PMID:18837079
  Authors
Esteller A
  Title
Physiology of bile secretion.
  Journal
World J Gastroenterol 14:5641-9 (2008)
DOI:10.3748/wjg.14.5641
Reference
PMID:12483266
  Authors
Takikawa H
  Title
Hepatobiliary transport of bile acids and organic anions.
  Journal
J Hepatobiliary Pancreat Surg 9:443-7 (2002)
DOI:10.1007/s005340200055
Reference
PMID:11316487
  Authors
St-Pierre MV, Kullak-Ublick GA, Hagenbuch B, Meier PJ
  Title
Transport of bile acids in hepatic and non-hepatic tissues.
  Journal
J Exp Biol 204:1673-86 (2001)
Reference
PMID:18670431
  Authors
Thomas C, Pellicciari R, Pruzanski M, Auwerx J, Schoonjans K
  Title
Targeting bile-acid signalling for metabolic diseases.
  Journal
Nat Rev Drug Discov 7:678-93 (2008)
DOI:10.1038/nrd2619
Reference
PMID:15975683
  Authors
Pauli-Magnus C, Stieger B, Meier Y, Kullak-Ublick GA, Meier PJ
  Title
Enterohepatic transport of bile salts and genetics of cholestasis.
  Journal
J Hepatol 43:342-57 (2005)
DOI:10.1016/j.jhep.2005.03.017
Reference
PMID:18081658
  Authors
Pellicoro A, Faber KN
  Title
Review article: The function and regulation of proteins involved in bile salt biosynthesis and transport.
  Journal
Aliment Pharmacol Ther 26 Suppl 2:149-60 (2007)
DOI:10.1111/j.1365-2036.2007.03522.x
Reference
PMID:19482594
  Authors
Jonker JW, Stedman CA, Liddle C, Downes M
  Title
Hepatobiliary ABC transporters: physiology, regulation and implications for disease.
  Journal
Front Biosci 14:4904-20 (2009)
DOI:10.2741/3576
Reference
PMID:19273385
  Authors
Modica S, Bellafante E, Moschetta A
  Title
Master regulation of bile acid and xenobiotic metabolism via the FXR, PXR and CAR trio.
  Journal
Front Biosci 14:4719-45 (2009)
DOI:10.2741/3563
Reference
PMID:16706681
  Authors
Cai SY, Boyer JL
  Title
FXR: a target for cholestatic syndromes?
  Journal
Expert Opin Ther Targets 10:409-21 (2006)
DOI:10.1517/14728222.10.3.409
Reference
PMID:19273238
  Authors
Ballatori N, Li N, Fang F, Boyer JL, Christian WV, Hammond CL
  Title
OST alpha-OST beta: a key membrane transporter of bile acids and conjugated steroids.
  Journal
Front Biosci 14:2829-44 (2009)
DOI:10.2741/3416
Reference
PMID:18377365
  Authors
Roma MG, Crocenzi FA, Sanchez Pozzi EA
  Title
Hepatocellular transport in acquired cholestasis: new insights into functional, regulatory and therapeutic aspects.
  Journal
Clin Sci (Lond) 114:567-88 (2008)
DOI:10.1042/CS20070227
Reference
PMID:18371245
  Authors
Arrese M, Macias RI, Briz O, Perez MJ, Marin JJ
  Title
Molecular pathogenesis of intrahepatic cholestasis of pregnancy.
  Journal
Expert Rev Mol Med 10:e9 (2008)
DOI:10.1017/S1462399408000628
Related
pathway
rno00120  Primary bile acid biosynthesis
rno04144  Endocytosis
rno04530  Tight junction
rno04975  Fat digestion and absorption
KO pathway
ko04976   
LinkDB

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