Downregulation of aquaporin-2 and -3 in aging kidney is independent of V(2) vasopressin receptor

Am J Physiol Renal Physiol. 2000 Jul;279(1):F144-52. doi: 10.1152/ajprenal.2000.279.1.F144.

Abstract

The mechanisms underlying age-related polyuria were investigated in 10- and 30-mo-old female WAG/Rij rats. Urinary volume and osmolality were 3.9 +/- 0.3 ml/24 h and 2,511 +/- 54 mosmol/kgH(2)O in adult rats and 12.8 +/- 0.8 ml/24 h and 1,042 +/- 44 mosmol/kgH(2)O in senescent animals. Vasopressin V(2) receptor mRNA did not significantly differ between 10 and 30 mo, and [(3)H]vasopressin binding sites in membrane papilla were reduced by 30%. The cAMP content of the papilla was unchanged with age, whereas papillary osmolality was significantly lowered in senescent animals. The expression of aquaporin-1 (AQP1) and -4 was mostly unaltered from 10 to 30 mo. In contrast, aquaporin-2 (AQP2) and -3 (AQP3) expression was downregulated by 80 and 50%, respectively, and AQP2 was markedly redistributed into the intracellular compartment, in inner medulla of senescent animals, but not in renal cortex. These results indicate that age-related polyuria is associated with a downregulation of AQP2 and AQP3 expression in the medullary collecting duct, which is independent of vasopressin-mediated cAMP accumulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Aquaporin 2
  • Aquaporin 3
  • Aquaporin 6
  • Aquaporins / metabolism*
  • Binding Sites
  • Body Weight
  • Cell Membrane / metabolism
  • Cyclic AMP / metabolism
  • Down-Regulation*
  • Drinking
  • Eating
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Kidney / metabolism*
  • Kidney / pathology
  • Kidney / physiopathology
  • Kidney / ultrastructure
  • Kidney Medulla / metabolism
  • Kidney Medulla / pathology
  • Kidney Medulla / physiopathology
  • Kidney Medulla / ultrastructure
  • Kidney Tubules / metabolism
  • Kidney Tubules / pathology
  • Kidney Tubules / physiopathology
  • Kidney Tubules / ultrastructure
  • Osmolar Concentration
  • Polyuria / metabolism*
  • Polyuria / pathology
  • Polyuria / physiopathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred Strains
  • Receptors, Vasopressin / genetics
  • Receptors, Vasopressin / metabolism*
  • Vasopressins / metabolism

Substances

  • Aqp2 protein, rat
  • Aqp3 protein, rat
  • Aquaporin 2
  • Aquaporin 6
  • Aquaporins
  • RNA, Messenger
  • Receptors, Vasopressin
  • Vasopressins
  • Aquaporin 3
  • Cyclic AMP