KEGG   PATHWAY: hsa04962
Entry
hsa04962                    Pathway                                
Name
Vasopressin-regulated water reabsorption - Homo sapiens (human)
Description
In the kidney, the antidiuretic hormone vasopressin (AVP) is a critical regulator of water homeostasis by controlling the water movement from lumen to the interstitium for water reabsorption and adjusting the urinary water excretion. In normal physiology, AVP is secreted into the circulation by the posterior pituitary gland, in response to an increase in serum osmolality or a decrease in effective circulating volume. When reaching the kidney, AVP binds to V2 receptors on the basolateral surface of the collecting duct epithelium, triggering a G-protein-linked signaling cascade, which leads to water channel aquaporin-2 (AQP2) vesicle insertion into the apical plasma membrane. This results in higher water permeability in the collecting duct and, driven by an osmotic gradient, pro-urinary water then passes the membrane through AQP2 and leaves the cell on the basolateral side via AQP3 and AQP4 water channels, which are constitutively expressed on the basolateral side of these cells. When isotonicity is restored, reduced blood AVP levels results in AQP2 internalization, leaving the apical membrane watertight again.
Class
Organismal Systems; Excretory system
Pathway map
hsa04962  Vasopressin-regulated water reabsorption
hsa04962

Network
  Element
N00915  AVP-V2R-PKA signaling pathway
Drug
D00101  Vasopressin (JP18/USP)
D00291  Desmopressin (INN)
D00366  Lypressin (USAN/INN)
D01213  Tolvaptan (JAN/USAN/INN)
D01236  Conivaptan hydrochloride (JAN/USAN)
D01855  Mozavaptane hydrochloride (JAN)
D02235  Desmopressin acetate (USP)
D02983  Argipressin tannate (USAN)
D04752  Lixivaptan (USAN/INN)
D06672  Terlipressin (USAN/INN)
D07227  Ornipressin (INN)
D07748  Conivaptan (INN)
D08571  Terlipressin acetate (JAN)
D09820  Vasopressin tannate (JAN)
D11659  Tolvaptan sodium phosphate (JAN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
551  AVP; arginine vasopressin [KO:K05242]
554  AVPR2; arginine vasopressin receptor 2 [KO:K04228]
2778  GNAS; GNAS complex locus [KO:K04632]
112  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
109  ADCY3; adenylate cyclase 3 [KO:K08043] [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]
397  ARHGDIB; Rho GDP dissociation inhibitor beta [KO:K12462]
396  ARHGDIA; Rho GDP dissociation inhibitor alpha [KO:K12462]
398  ARHGDIG; Rho GDP dissociation inhibitor gamma [KO:K12462]
1385  CREB1; cAMP responsive element binding protein 1 [KO:K05870]
10488  CREB3; cAMP responsive element binding protein 3 [KO:K09048]
90993  CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048]
64764  CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048]
84699  CREB3L3; cAMP responsive element binding protein 3 like 3 [KO:K09048]
148327  CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048]
9586  CREB5; cAMP responsive element binding protein 5 [KO:K09047]
359  AQP2; aquaporin 2 [KO:K09865]
8766  RAB11A; RAB11A, member RAS oncogene family [KO:K07904]
9230  RAB11B; RAB11B, member RAS oncogene family [KO:K07905]
1778  DYNC1H1; dynein cytoplasmic 1 heavy chain 1 [KO:K10413]
79659  DYNC2H1; dynein cytoplasmic 2 heavy chain 1 [KO:K10414]
1780  DYNC1I1; dynein cytoplasmic 1 intermediate chain 1 [KO:K10415]
1781  DYNC1I2; dynein cytoplasmic 1 intermediate chain 2 [KO:K10415]
1783  DYNC1LI2; dynein cytoplasmic 1 light intermediate chain 2 [KO:K10416]
51143  DYNC1LI1; dynein cytoplasmic 1 light intermediate chain 1 [KO:K10416]
51626  DYNC2LI1; dynein cytoplasmic 2 light intermediate chain 1 [KO:K10417]
8655  DYNLL1; dynein light chain LC8-type 1 [KO:K10418]
140735  DYNLL2; dynein light chain LC8-type 2 [KO:K10418]
1639  DCTN1; dynactin subunit 1 [KO:K04648]
10540  DCTN2; dynactin subunit 2 [KO:K10424]
51164  DCTN4; dynactin subunit 4 [KO:K10426]
84516  DCTN5; dynactin subunit 5 [KO:K10427]
10671  DCTN6; dynactin subunit 6 [KO:K10428]
6844  VAMP2; vesicle associated membrane protein 2 [KO:K13504]
4905  NSF; N-ethylmaleimide sensitive factor, vesicle fusing ATPase [KO:K06027] [EC:3.6.4.6]
6810  STX4; syntaxin 4 [KO:K13502]
5868  RAB5A; RAB5A, member RAS oncogene family [KO:K07887]
5869  RAB5B; RAB5B, member RAS oncogene family [KO:K07888]
5878  RAB5C; RAB5C, member RAS oncogene family [KO:K07889]
361  AQP4; aquaporin 4 [KO:K09866]
360  AQP3; aquaporin 3 (Gill blood group) [KO:K09876]
Compound
C00001  H2O
C00575  3',5'-Cyclic AMP
Reference
  Authors
Boone M, Deen PM
  Title
Physiology and pathophysiology of the vasopressin-regulated renal water reabsorption.
  Journal
Pflugers Arch 456:1005-24 (2008)
DOI:10.1007/s00424-008-0498-1
Reference
  Authors
Takata K, Matsuzaki T, Tajika Y, Ablimit A, Hasegawa T
  Title
Localization and trafficking of aquaporin 2 in the kidney.
  Journal
Histochem Cell Biol 130:197-209 (2008)
DOI:10.1007/s00418-008-0457-0
Reference
  Authors
Nielsen S, Kwon TH, Christensen BM, Promeneur D, Frokiaer J, Marples D
  Title
Physiology and pathophysiology of renal aquaporins.
  Journal
J Am Soc Nephrol 10:647-63 (1999)
Reference
  Authors
Marples D, Frokiaer J, Nielsen S
  Title
Long-term regulation of aquaporins in the kidney.
  Journal
Am J Physiol 276:F331-9 (1999)
DOI:10.1152/ajprenal.1999.276.3.F331
Reference
  Authors
Ward DT, Hammond TG, Harris HW
  Title
Modulation of vasopressin-elicited water transport by trafficking of aquaporin2-containing vesicles.
  Journal
Annu Rev Physiol 61:683-97 (1999)
DOI:10.1146/annurev.physiol.61.1.683
Reference
  Authors
Fenton RA, Moeller HB
  Title
Recent discoveries in vasopressin-regulated aquaporin-2 trafficking.
  Journal
Prog Brain Res 170:571-9 (2008)
DOI:10.1016/S0079-6123(08)00444-5
Reference
  Authors
Nielsen S, Frokiaer J, Marples D, Kwon TH, Agre P, Knepper MA
  Title
Aquaporins in the kidney: from molecules to medicine.
  Journal
Physiol Rev 82:205-44 (2002)
DOI:10.1152/physrev.00024.2001
Reference
  Authors
Deen PM, van Balkom BW, Kamsteeg EJ
  Title
Routing of the aquaporin-2 water channel in health and disease.
  Journal
Eur J Cell Biol 79:523-30 (2000)
DOI:10.1078/0171-9335-00075
Reference
  Authors
Bonilla-Felix M
  Title
Development of water transport in the collecting duct.
  Journal
Am J Physiol Renal Physiol 287:F1093-101 (2004)
DOI:10.1152/ajprenal.00119.2004
Reference
  Authors
Uawithya P, Pisitkun T, Ruttenberg BE, Knepper MA
  Title
Transcriptional profiling of native inner medullary collecting duct cells from rat kidney.
  Journal
Physiol Genomics 32:229-53 (2008)
DOI:10.1152/physiolgenomics.00201.2007
Reference
  Authors
Nguyen MK, Nielsen S, Kurtz I
  Title
Molecular pathogenesis of nephrogenic diabetes insipidus.
  Journal
Clin Exp Nephrol 7:9-17 (2003)
DOI:10.1007/s101570300001
Related
pathway
hsa04144  Endocytosis
hsa04530  Tight junction
KO pathway
ko04962   
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