title: Vasopressin stimulates Na-dependent phosphate transport and calcification in rat aortic smooth muscle cells.
abstract: We investigated the effect of arginine vasopressin (AVP) on inorganic phosphate (Pi) transport in A-10 rat aortic vascular smooth muscle cells (VSMCs). AVP time- and dose-dependently stimulated Na-dependent Pi transport in A-10 cells. This stimulatory effect of AVP on Pi transport was markedly suppressed by V1 receptor antagonist. A protein kinase C (PKC) inhibitor calphostin C partially suppressed the stimulatory effect of AVP. The selective inhibitors of c-Jun-NH2-terminal mitogen-activated protein (MAP) kinase (Jun kinase) attenuated AVP-induced Pi transport, but Erk kinase or p38 MAP kinase inhibitors did not. Wortmannin, a phosphatidylinositol (PI) 3-kinase inhibitor, suppressed AVP-induced Pi transport. Rapamycin, a selective inhibitor of S6 kinase, reduced this effect of AVP, while Akt kinase inhibitor did not. The combination of inhibitors for PKC, Jun kinase and PI 3-kinase completely suppressed the AVP-enhanced Pi transport. Furthermore, AVP rescued the VSMC from high phosphate-induced cell death and enhanced mineralization of these cells. In summary, these results suggest that AVP stimulates both Na-dependent Pi transport and mineralization in VSMCs. The mechanism is mediated by the activation of multiple signaling pathways including PKC, PI 3-kinase, S6 kinase and Jun kinase.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Nishiwaki-Yasuda
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suzuki
authors.forename: Ayako
authors.initials: A
authors.lastname: Kakita
authors.forename: Sahoko
authors.initials: S
authors.lastname: Sekiguchi
authors.forename: Shogo
authors.initials: S
authors.lastname: Asano
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nishii
authors.forename: Shizuko
authors.initials: S
authors.lastname: Nagao
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Oiso
authors.forename: Mitsuyasu
authors.initials: M
authors.lastname: Itoh
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002114:Calcinosis / Q000139:chemically induced*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000166:cytology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors / Q000502:physiology; D010710:Phosphates / Q000378:metabolism*; D051381:Rats; D050608:Sodium-Phosphate Cotransporter Proteins / Q000378:metabolism*; D013997:Time Factors; D014652:Vascular Diseases / Q000139:chemically induced*
chemical_list: D010710:Phosphates; D050608:Sodium-Phosphate Cotransporter Proteins; D001127:Arginine Vasopressin; D051058:Oncogene Protein v-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium