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


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.

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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.

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Correspondence to Kristian Vinter Juul.

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Juul, K.V. The evolutionary origin of the vasopressin/V2-type receptor/aquaporin axis and the urine-concentrating mechanism. Endocrine 42, 63–68 (2012).

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  • Arginine vasopressin
  • V2-R
  • AQPs
  • Evolution