title: Aldosterone requires vasopressin V1a receptors on intercalated cells to mediate acid-base homeostasis.
abstract: Both aldosterone and luminal vasopressin may contribute to the maintenance of acid-base homeostasis, but the functional relationship between these hormones is not well understood. The effects of luminal vasopressin likely result from its interaction with V1a receptors on the luminal membranes of intercalated cells in the collecting duct. Here, we found that mice lacking the V1a receptor exhibit type 4 renal tubular acidosis. The administration of the mineralocorticoid agonist fludrocortisone ameliorated the acidosis by restoring excretion of urinary ammonium via increased expression of Rhcg and H-K-ATPase and decreased expression of H-ATPase. In a cell line of intercalated cells established from transgenic rats expressing the mineralocorticoid and V1a receptors, but not V2 receptors, knockdown of the V1a receptor gene abrogated the effects of aldosterone on H-K-ATPase, Rhcg, and H-ATPase expression. These data suggest that defects in the vasopressin V1a receptor in intercalated cells can cause type 4 renal tubular acidosis and that the tubular effects of aldosterone depend on a functional V1a receptor in the intercalated cells.
authors.affiliation: Department of Nephrology, Graduate School of Faculty of Life Science, Kumamoto University, Kumamoto, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Izumi
authors.forename: Kahori
authors.initials: K
authors.lastname: Hori
authors.forename: Yushi
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Miho
authors.initials: M
authors.lastname: Kimura
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Hasuike
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Nanami
authors.forename: Yukimasa
authors.initials: Y
authors.lastname: Kohda
authors.forename: Yoshinaga
authors.initials: Y
authors.lastname: Otaki
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kuragano
authors.forename: Masuo
authors.initials: M
authors.lastname: Obinata
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Kawahara
authors.forename: Akito
authors.initials: A
authors.lastname: Tanoue
authors.forename: Kimio
authors.initials: K
authors.lastname: Tomita
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakanishi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nonoguchi
mesh_terms: D000136:Acid-Base Equilibrium / Q000187:drug effects / Q000502:physiology*; D000450:Aldosterone / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D027682:Cation Transport Proteins / Q000378:metabolism; D002460:Cell Line; D005438:Fludrocortisone / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008901:Mineralocorticoids / Q000819:agonists; D023421:Models, Animal; D006180:Proton-Translocating ATPases / Q000378:metabolism; D034622:RNA Interference; D051381:Rats; D055647:Rats, Transgenic; D017483:Receptors, Vasopressin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D027682:Cation Transport Proteins; D008562:Membrane Glycoproteins; D008901:Mineralocorticoids; D017483:Receptors, Vasopressin; C508143:Rh type C glycoprotein, rat; C485880:Rhcg protein, mouse; D000450:Aldosterone; D006180:Proton-Translocating ATPases; D005438:Fludrocortisone