Vasopressin-regulated water reabsorption (WP5085)

Homo sapiens

This pathway describes Vasopressin-regulated water reabsorption from the kidney tubules of the nephrons back into the circulation. Vasopressin, antidiuretic hormone (ADH), is a peptide hormone produced in neurons of the hypothalamus in response to changes in response to extracellular fluid hypertonicity (hyperosmolality), and is secreted into the circulation. When it reaches the kidney, it binds to Vasopressin 2 receptors, triggering an intracellular signaling cascade that ultimately leads to aquaporin 2 (AQP2) vesicles inserted in the apical membrane. This increases the water permeability of the membrane. An osmotic gradient then drives water transport from the collecting duct through AQP2, and water exits the cell on the basolateral side, and back into the circulation. This description was adapted from [ Wikipedia] and [ KEGG]. This pathway was modeled from [ KEGG].


Kristina Hanspers


last edited

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Homo sapiens



Pathway Ontology

vasopressin signaling pathway water transport pathway

Cell Type Ontology

kidney cell


Label Type Compact URI Comment
cAMP Metabolite hmdb:HMDB00058
Water Metabolite hmdb:HMDB02111
Water Metabolite hmdb:HMDB02111
Water Metabolite hmdb:HMDB02111
Water Metabolite hmdb:HMDB02111
RAB11A GeneProduct ensembl:ENSG00000103769
STX4 GeneProduct ensembl:ENSG00000103496
RAB5A GeneProduct ensembl:ENSG00000144566
AQP3 GeneProduct ensembl:ENSG00000165272
PRKACA GeneProduct ensembl:ENSG00000072062
GNAS GeneProduct ensembl:ENSG00000087460
AQP2 GeneProduct ensembl:ENSG00000167580
ARHGDIA GeneProduct ensembl:ENSG00000141522
DCTN2 GeneProduct ensembl:ENSG00000175203
AVP GeneProduct ensembl:ENSG00000101200
ADCY3 GeneProduct ensembl:ENSG00000138031
RAB11B GeneProduct ensembl:ENSG00000185236
PRKACB GeneProduct ensembl:ENSG00000142875
PRKACG GeneProduct ensembl:ENSG00000165059
CREB3 GeneProduct ensembl:ENSG00000107175 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:12913
CREB1 GeneProduct ensembl:ENSG00000118260 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:12912
CREB3L2 GeneProduct ensembl:ENSG00000182158 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:208647
CREB3L3 GeneProduct ensembl:ENSG00000060566 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:208677
CREB3L1 GeneProduct ensembl:ENSG00000157613 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:26427
CREB3L4 GeneProduct ensembl:ENSG00000143578 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:78284
CREB5 GeneProduct ensembl:ENSG00000146592 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:231991
DYNC2H1 GeneProduct ensembl:ENSG00000187240
DYNC2LI1 GeneProduct ensembl:ENSG00000138036
DYNLL2 GeneProduct ensembl:ENSG00000264364
DYNLL1 GeneProduct ensembl:ENSG00000088986
DYNC1LI1 GeneProduct ensembl:ENSG00000144635
DYNC1I2 GeneProduct ensembl:ENSG00000077380
DYNC1I1 GeneProduct ensembl:ENSG00000158560
DYNC1LI2 GeneProduct ensembl:ENSG00000135720
DYNC1H1 GeneProduct ensembl:ENSG00000197102
DCTN4 GeneProduct ensembl:ENSG00000132912
DCTN1 GeneProduct ensembl:ENSG00000204843
DCTN5 GeneProduct ensembl:ENSG00000166847
DCTN6 GeneProduct ensembl:ENSG00000104671
VAMP2 GeneProduct ensembl:ENSG00000220205
NSF GeneProduct ensembl:ENSG00000073969
AQP2 GeneProduct ensembl:ENSG00000167580
AQP2 GeneProduct ensembl:ENSG00000167580
AQP2 GeneProduct ensembl:ENSG00000167580
ADCY6 GeneProduct ensembl:ENSG00000174233
ADCY9 GeneProduct ensembl:ENSG00000162104
ARHGDIB GeneProduct ensembl:ENSG00000111348
ARHGDIG GeneProduct ensembl:ENSG00000242173
AVPR2 GeneProduct ensembl:ENSG00000126895
AQP4 GeneProduct ensembl:ENSG00000171885
AQP3 GeneProduct ensembl:ENSG00000165272
AQP2 GeneProduct ensembl:ENSG00000167580
RAB5B GeneProduct ensembl:ENSG00000111540
RAB5C GeneProduct ensembl:ENSG00000108774
AQP2 GeneProduct ensembl:ENSG00000167580


  1. Long-term regulation of aquaporins in the kidney. Marples D, Frøkiaer J, Nielsen S. Am J Physiol. 1999 Mar;276(3):F331-9. PubMed Europe PMC Scholia
  2. Physiology and pathophysiology of renal aquaporins. Nielsen S, Kwon TH, Christensen BM, Promeneur D, Frøkiaer J, Marples D. J Am Soc Nephrol. 1999 Mar;10(3):647–63. PubMed Europe PMC Scholia
  3. Modulation of vasopressin-elicited water transport by trafficking of aquaporin2-containing vesicles. Ward DT, Hammond TG, Harris HW. Annu Rev Physiol. 1999;61:683–97. PubMed Europe PMC Scholia
  4. Routing of the aquaporin-2 water channel in health and disease. Deen PM, van Balkom BW, Kamsteeg EJ. Eur J Cell Biol. 2000 Aug;79(8):523–30. PubMed Europe PMC Scholia
  5. Aquaporins in the kidney: from molecules to medicine. Nielsen S, Frøkiaer J, Marples D, Kwon TH, Agre P, Knepper MA. Physiol Rev. 2002 Jan;82(1):205–44. PubMed Europe PMC Scholia
  6. Molecular pathogenesis of nephrogenic diabetes insipidus. Nguyen MK, Nielsen S, Kurtz I. Clin Exp Nephrol. 2003 Mar;7(1):9–17. PubMed Europe PMC Scholia
  7. Development of water transport in the collecting duct. Bonilla-Felix M. Am J Physiol Renal Physiol. 2004 Dec;287(6):F1093-101. PubMed Europe PMC Scholia
  8. Transcriptional profiling of native inner medullary collecting duct cells from rat kidney. Uawithya P, Pisitkun T, Ruttenberg BE, Knepper MA. Physiol Genomics. 2008 Jan 17;32(2):229–53. PubMed Europe PMC Scholia
  9. Physiology and pathophysiology of the vasopressin-regulated renal water reabsorption. Boone M, Deen PMT. Pflugers Arch. 2008 Sep;456(6):1005–24. PubMed Europe PMC Scholia
  10. Localization and trafficking of aquaporin 2 in the kidney. Takata K, Matsuzaki T, Tajika Y, Ablimit A, Hasegawa T. Histochem Cell Biol. 2008 Aug;130(2):197–209. PubMed Europe PMC Scholia
  11. Recent discoveries in vasopressin-regulated aquaporin-2 trafficking. Fenton RA, Moeller HB. Prog Brain Res. 2008;170:571–9. PubMed Europe PMC Scholia