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Sustained Elevated Levels of Circulating Vasopressin Selectively Stimulate the Proliferation of Kidney Tubular Cells via the Activation of V₂ Receptors

Départements d’Endocrinologie (G.A., E.G., V.B., A.G., G.G.) and Neurobiologie (A.J., V.C.), Institut de Génomique Fonctionnelle, Centre National de la Recherche Scientifique Unit Mixté de Recherche 5203 (G.A., E.G., V.B., A.G., A.J., V.C., G.G.), Institut National de la Santé et de la Recherche Médicale Unité 661 (G.A., E.G., V.B., A.G., A.J., V.C., G.G.), and Université Montpellier I and Université Montpellier II (G.A., E.G., V.B., A.G., A.J., V.C., G.G.), F-34094 Montpellier, France

Address all correspondence and requests for reprints to: Gilles Guillon, Institut de Génomique Fonctionnelle, 141 Rue de la Cardonille, 34094 Montpellier cedex 05, France. E-mail: gilles.guillon{at}igf.cnrs.fr.

The hypothalamic hormone vasopressin (AVP) has known mitogenic effects on various cell types. This study was designed to determine whether sustained elevated levels of circulating AVP could influence cell proliferation within adult tissues known to express different AVP receptors, including the pituitary, adrenal gland, liver, and kidney. Plasmatic AVP was chronically increased by submitting animals to prolonged hyperosmotic stimulation or implanting them with a AVP-containing osmotic minipump. After several days of either treatment, increased cell proliferation was detected only within the kidney. This kidney cell proliferation was not affected by the administration of selective V_1a or V_1b receptor antagonists but was either inhibited or mimicked by the administration of a selective V₂ receptor antagonist or agonist, respectively. Kidney proliferative cells mostly concerned a subpopulation of differentiated tubular cells known to express the V₂ receptors and were associated with the phosphorylation of ERK. These data indicate that in the adult rat, sustained elevated levels of circulating AVP stimulates the proliferation of a subpopulation of kidney tubular cells expressing the V₂ receptor, providing the first illustration of a mitogenic effect of AVP via the activation of the V₂ receptor subtype.

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