Skip to main content
Log in

The evolutionary origin of the vasopressin/V2-type receptor/aquaporin axis and the urine-concentrating mechanism

  • Mini Review
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

In this mini-review, current evidence for how the vasopressin/V2-type receptor/aquaporin axis developed co-evolutionary as a crucial part of the urine-concentrating mechanism will be presented. The present-day human kidney, allowing the concentration of urine up to a maximal osmolality around 1200 mosmol kg−1—or urine to plasma osmolality ratio around 4—with essentially no sodium secreted is the result of up to 3 billion years evolution. Moving from aquatic to terrestrial habitats required profound changes in kidney morphology, most notable the loops of Henle modifying the kidneys from basically a water excretory system to a water conserving system. Vasopressin-like molecules has during the evolution played a significant role in body fluid homeostasis, more specifically, the osmolality of body liquids by controlling the elimination/reabsorption of fluid trough stimulating V2-type receptors to mobilize aquaporin water channels in the renal collector tubules. Recent evidence supports that all components of the vasopressin/V2-type receptor/aquaporin axis can be traced back to early precursors in evolutionary history. The potential clinical and pharmacological implications of a better phylogenetic understanding of these biological systems so essential for body fluid homeostasis relates to any pathological aspects of the urine-concentrating mechanism, in particular deficiencies of any part of the vasopressin-V2R-AQP2 axis causing central or nephrogenic diabetes insipidus—and for broader patient populations also in preventing and treating disturbances in human circadian regulation of urine volume and osmolality that may lead to enuresis and nocturia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. H.W. Smith, From Fish to Philosopher (Summit, Ciba, 1959)

    Google Scholar 

  2. J.M. Sands, J.P. Kokko, Countercurrent system. Kidney Int. 38(4), 695–699 (1990)

    Article  PubMed  CAS  Google Scholar 

  3. C. Esteva-Font, J. Ballarin, P. Fernández-Llama, Molecular biology of water and salt regulation in the kidney. Cell Mol. Life Sci. 69(5), 683–695 (2012)

    Google Scholar 

  4. G.J. Roch, E.R. Busby, N.M. Sherwood, Evolution of GnRH: diving deeper. Gen. Comp. Endocrinol. 171(1), 1–16 (2011). Epub 2010 Dec 23

    Article  PubMed  CAS  Google Scholar 

  5. G.L. Robertson, Antidiuretic hormone: normal and disordered function. Endocrinol. Metab. Clin. North Am. 30, 671–694 (2001)

    Article  PubMed  CAS  Google Scholar 

  6. C.F. Ferris, Vasopressin/oxytocin and aggression. Novartis Found. Symp. 268, 190–8 (2005). discussion 198–200, 242–53

    Google Scholar 

  7. E.K. Jackson, Vasopressin and Other Agents Affecting the Renal Conservation of Water, in Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 11th edn., ed. by L.L. Brunton, J.S. Lazo, K.L. Parker (McGraw-Hill, Inc., New York, 2001), pp. 771–788

    Google Scholar 

  8. C.H. Hoyle, Neuropeptide families: evolutionary perspectives. Regul. Pept. 73, 1–33 (1998)

    Article  PubMed  CAS  Google Scholar 

  9. R. Acher, J. Chauvet, The neurohypophysial endocrine regulatory cascade: precursors, mediators, receptors, and effectors. Front. Neuroendocrinol. 16(3), 237–289 (1995)

    Article  PubMed  CAS  Google Scholar 

  10. H. Minakata, Oxytocin/vasopressin and gonadotropin-releasing hormone from cephalopods to vertebrates. Ann. N. Y. Acad. Sci. 1200, 33–42 (2010)

    Article  PubMed  CAS  Google Scholar 

  11. R. Acher, Molecular evolution of biologically active polypeptides. Proc. R. Soc. Lond. B Biol. Sci. 210, 21–43 (1980)

    Article  PubMed  CAS  Google Scholar 

  12. S. Hyodo, Y. Kato, M. Ono, A. Urano, Cloning and sequence analyses of cDNAs encoding vasotocin and isotocin precursors of chum salmon, Oncorhynchus keta: evolutionary relationships of neurohypophysial hormone precursors. J. Comp. Physiol. B. 160, 601–608 (1991)

    Article  PubMed  CAS  Google Scholar 

  13. B.B. McEwen, General introduction to vasopressin and oxytocin: Structure/metabolism, evolutionary aspects, neural pathway/receptor distribution, and functional aspects relevant to memory processing. Adv. Pharmacol. 50, 1–50 (2004)

    Article  PubMed  Google Scholar 

  14. Y.V. Natochin, E.I. Shakhmatova, The origin of the hydroosmotic effect of arginine vasopressin: a hypothesis. Dokl. Biol. Sci. 389, 96–98 (2003)

    Article  PubMed  CAS  Google Scholar 

  15. Y. Takei, A. Kawakoshi, T. Tsukada, S. Yuge, M. Ogoshi, K. Inoue, S. Hyodo, H. Bannai, S. Miyano, Contribution of comparative fish studies to general endocrinology: structure and function of some osmoregulatory hormones. J Exp Zool A Comp Exp Biol. 305(9), 787–798 (2006)

    PubMed  Google Scholar 

  16. L. Abrami, R. Gobin, V. Berthonaud, H.L. Thanh, J. Chevalier, P. Ripoche, J.M. Verbavatz, Localization of the FA-CHIP water channel in frog urinary bladder. Eur. J. Cell Biol. 73(3), 215–221 (1997)

    PubMed  CAS  Google Scholar 

  17. S.O. Kim, S.H. Song, E.C. Hwang, K.J. Oh, K. Ahn, S.I. Jung, T.W. Kang, D. Kwon, K. Park, S.B. Ryu, Changes in aquaporin (AQP)2 and AQP3 expression in ovariectomized rat urinary bladder: potential implication of water permeability in urinary bladder. World J. Urol. (2011). doi:10.1007/s00345-011-0674-3

  18. I. Böselt, H. Römpler, T. Hermsdorf, D. Thor, W. Busch, A. Schulz, T. Schöneberg, Involvement of the V2 vasopressin receptor in adaptation to limited water supply. PLoS One 4(5), e5573 (2009)

    Article  PubMed  Google Scholar 

  19. C. Barberis, B. Mouillac, T. Durroux, Structural bases of vasopressin/oxytocin receptor function. J. Endocrinol. 156, 223–229 (1998)

    Article  PubMed  CAS  Google Scholar 

  20. G. Heckel, S. Fink, Evolution of the arginine vasopressin 1a receptor and implications for mammalian social behaviour. Prog. Brain Res. 170, 321–330 (2008)

    Article  PubMed  CAS  Google Scholar 

  21. S. Nielsen, D. Marples, J. Frokiaer, M. Knepper, P. Agre, The aquaporin family of water channels in kidney: an update on physiology and pathophysiology of aquaporin-2. Kidney Int. 49, 1718–1723 (1996)

    Article  PubMed  CAS  Google Scholar 

  22. C.E. Gustafson, T. Katsura, M. McKee, R. Bouley, J.E. Casanova, D. Brown, Recycling of AQP2 occurs through a temperature- and bafilomycin-sensitive trans-Golgi-associated compartment. Am. J. Physiol. Renal Physiol. 278, F317–F326 (2000)

    PubMed  CAS  Google Scholar 

  23. T.X. Sun, A. Van Hoek, Y. Huang, R. Bouley, M. McLaughlin, D. Brown, Aquaporin-2 localization in clathrin-coated pits: inhibition of endocytosis by dominant-negative dynamin. Am. J. Physiol. Renal Physiol. 282, F998–F1011 (2002)

    PubMed  CAS  Google Scholar 

  24. H. Lu, T.X. Sun, R. Bouley, K. Blackburn, M. McLaughlin, D. Brown, Inhibition of endocytosis causes phosphorylation (S256)-independent plasma membrane accumulation of AQP2. Am. J. Physiol. Renal Physiol. 286, F233–F243 (2004)

    Article  PubMed  CAS  Google Scholar 

  25. G.L. Robertson, Disorders of water balance, in Clinical Pediatric Endocrinology, 4th edn., ed. by C.G.D. Brook, P.C. Hindmarsch (Blackwell Science, Oxford, 2001), pp. 193–221

    Google Scholar 

  26. K.V. Juul, D.G. Bichet, J.P. Nørgaard, Desmopressin duration of antidiuretic action in patients with central diabetes insipidus. Endocrine 40(1), 67–74 (2011)

    Article  PubMed  CAS  Google Scholar 

  27. N. Nakamura, Reduced aldehyde dehydrogenase activity and arginine vasopressin receptor 2 expression in the kidneys of male TALLYHO/JngJ mice of prediabetic age. Endocrine 40(3), 379–385 (2011)

    Article  PubMed  CAS  Google Scholar 

  28. T. Sahakitrungruang, S. Wacharasindhu, T. Sinthuwiwat, V. Supornsilchai, K. Suphapeetiporn, V. Shotelersuk, Identification of two novel aquaporin-2 mutations in a Thai girl with congenital nephrogenic diabetes insipidus. Endocrine 33(2), 210–214 (2008)

    Article  PubMed  CAS  Google Scholar 

  29. S. Nielsen, P. Agre, The aquaporin family of water channels in kidney. Kidney Int. 48(4), 1057–1068 (1995)

    Article  PubMed  CAS  Google Scholar 

  30. R.N. Finn, J. Cerdà, Aquaporin evolution in fishes. Front Physiol. 2, 44 (2011)

    Article  PubMed  CAS  Google Scholar 

  31. J.B. Heymann, A. Engel, Aquaporins: phylogeny, structure, and physiology of water channels. News Physiol. Sci. 14, 187–193 (1999)

    PubMed  CAS  Google Scholar 

  32. K. Murata, K. Mitsuoka, T. Hirai, T. Walz, P. Agre, J.B. Heymann, A. Engel, Y. Fujiyoshi, Structural determinants of water permeation through aquaporin-1. Nature 407(6804), 599–605 (2000)

    Article  PubMed  CAS  Google Scholar 

  33. D.X. Fu, A. Libson, L.J.W. Miercke, C. Weitzman, P. Nollert, J. Krucinski, R.M. Stroud, Structure of a glycerol-conducting channel and the basis for its selectivity. Science 290, 481–486 (2000)

    Article  PubMed  CAS  Google Scholar 

  34. E. Kruse, N. Uehlein, R. Kaldenhoff, The aquaporins. Genome Biol. 7(2), 206 (2006). Epub 2006 Feb 28

    Article  PubMed  Google Scholar 

  35. B. Wu, C. Steinbronn, M. Alsterfjord, T. Zeuthen, E. Beitz, Concerted action of two cation filters in the aquaporin water channel. EMBO J. 28, 2188–2194 (2009)

    Article  PubMed  CAS  Google Scholar 

  36. L.S. King, D. Kozono, P. Agre, From structure to disease: the evolving tale of aquaporin biology. Natl. Rev. Mol. Cell. Biol. 5(9), 687–698 (2004)

    Article  CAS  Google Scholar 

  37. K. Ishibashi, S. Kondo, S. Hara, Y. Morishita, The evolutionary aspects of aquaporin family. Am. J. Physiol. Regul. Integr. Comp. Physiol. 300(3), R566–R576 (2011). Epub 2010 Dec 9

    Article  PubMed  CAS  Google Scholar 

  38. D. Gomes, A. Agasse, P. Thiébaud, S. Delrot, H. Gerós, F. Chaumont, Aquaporins are multifunctional water and solute transporters highly divergent in living organisms. Biochim. Biophys. Acta 1788(6), 1213–1228 (2009). Epub 2009 Mar 25

    Article  PubMed  CAS  Google Scholar 

  39. E.M. Campbell, A. Ball, S. Hoppler, A.S. Bowman, Invertebrate aquaporins: a review. J. Comp. Physiol. 178, 935–955 (2008)

    CAS  Google Scholar 

  40. D. Gorelick, J. Praetorius, T. Tsunenari, S. Nielsen, P. Agre, Aquaporin-11: a channel protein lacking apparent transport function expressed in brain. BMC Biochem. 7, 14 (2006)

    Article  PubMed  Google Scholar 

  41. S. Chanprasertyothin, S. Saetung, R. Rajatanavin, B. Ongphiphadhanakul, Genetic variant in the aquaporin 9 gene is associated with bone mineral density in postmenopausal women. Endocrine 38(1), 83–86 (2010). Epub 2010 Jun 18

    Article  PubMed  CAS  Google Scholar 

  42. S. Nielsen, S.R. DiGiovanni, E.I. Christensen et al., Cellular and subcellular immunolocalization of vasopressin-regulated water channel in rat kidney. Proc. Natl. Acad. Sci. USA 90, 11663–11667 (1993)

    Article  PubMed  CAS  Google Scholar 

  43. N. Konno, S. Hyodo, Y. Yamaguchi, K. Matsuda, M. Uchiyama, Vasotocin/V2-type receptor/aquaporin axis exists in African lungfish kidney but is functional only in terrestrial condition. Endocrinology 151(3), 1089–1096 (2010)

    Article  PubMed  CAS  Google Scholar 

  44. Y. Kondo, T. Morimoto, T. Nishio, U.F. Aslanova, M. Nishino, E.I. Farajov, N. Sugawara, N. Kumagai, A. Ohsaga, Y. Maruyama, S. Takahashi, Phylogenetic, ontogenetic, and pathological aspects of the urine-concentrating mechanism. Clin. Exp. Nephrol. 10(3), 165–174 (2006)

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The author would like to acknowledge and to express gratitude to my mentor, Professor Jens Peter Nørgaard, for encouraging this study and suggesting significant improvements of early drafts of this mini-review.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kristian Vinter Juul.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Juul, K.V. The evolutionary origin of the vasopressin/V2-type receptor/aquaporin axis and the urine-concentrating mechanism. Endocrine 42, 63–68 (2012). https://doi.org/10.1007/s12020-012-9634-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-012-9634-y

Keywords

Navigation