Downregulation of aquaporin-2 and -3 in aging kidney is independent of V(2) vasopressin receptor.
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.
Preisser
L
L
Service de Biologie Cellulaire, Commissariat à l'Energie Atomique/Saclay, Gif-sur-Yvette, France.
Teillet
L
L
Aliotti
S
S
Gobin
R
R
Berthonaud
V
V
Chevalier
J
J
Corman
B
B
Verbavatz
J M
JM
D000375:Aging / Q000502:physiology*; D000818:Animals; D051399:Aquaporin 2; D051400:Aquaporin 3; D051403:Aquaporin 6; D020346:Aquaporins / Q000378:metabolism*; D001665:Binding Sites; D001835:Body Weight; D002462:Cell Membrane / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D015536:Down-Regulation; D004326:Drinking; D004435:Eating; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D007668:Kidney / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D007679:Kidney Medulla / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D009994:Osmolar Concentration; D011141:Polyuria / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D017483:Receptors, Vasopressin / Q000235:genetics / Q000378:metabolism*; D014667:Vasopressins / Q000378:metabolism
C496025:Aqp2 protein, rat; C496029:Aqp3 protein, rat; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D012333:RNA, Messenger; D017483:Receptors, Vasopressin; D014667:Vasopressins; D051400:Aquaporin 3; D000242:Cyclic AMP