Molecular mechanisms of antidiuretic effect of oxytocin.
Oxytocin is known to have an antidiuretic effect, but the mechanisms underlying this effect are not completely understood. We infused oxytocin by osmotic minipump into vasopressin-deficient Brattleboro rats for five days and observed marked antidiuresis, increased urine osmolality, and increased solute-free water reabsorption. Administration of oxytocin also significantly increased the protein levels of aquaporin-2 (AQP2), phosphorylated AQP2 (p-AQP2), and AQP3 in the inner medulla and in the outer medulla plus cortex. Immunohistochemistry demonstrated increased AQP2 and p-AQP2 expression and trafficking to the apical plasma membrane of principal cells in the collecting duct, and increased AQP3 expression in the basolateral membrane. These oxytocin-induced effects were blocked by treatment with the vasopressin V2 receptor antagonist SR121463B, but not by treatment with the oxytocin receptor antagonist GW796679X. We conclude that vasopressin V2 receptors mediate the antidiuretic effects of oxytocin, including increased expression and apical trafficking of AQP2, p-AQP2, and increased AQP3 protein expression.
Department of Medicine, University of Colorado School of Medicine, Denver, Colorado, USA.
Chunling
C
Li
Weidong
W
Wang
Sandra N
SN
Summer
Timothy D
TD
Westfall
David P
DP
Brooks
Sandor
S
Falk
Robert W
RW
Schrier
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D051399:Aquaporin 2 / Q000378:metabolism; D051400:Aquaporin 3 / Q000378:metabolism; D004231:Diuresis / Q000187:drug effects / Q000502:physiology*; D007671:Kidney Concentrating Ability / Q000187:drug effects / Q000502:physiology*; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010121:Oxytocin / Q000494:pharmacology / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011910:Rats, Brattleboro; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000378:metabolism; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology
D065092:Antidiuretic Hormone Receptor Antagonists; C496025:Aqp2 protein, rat; C496029:Aqp3 protein, rat; D051399:Aquaporin 2; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; D051400:Aquaporin 3; D010121:Oxytocin