Vasopressin stimulates Na-dependent phosphate transport and calcification in rat aortic smooth muscle cells.
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.
Nishiwaki-Yasuda
Keiko
K
Division of Endocrinology and Metabolism, Department of Internal Medicine, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
Suzuki
Atsushi
A
Kakita
Ayako
A
Sekiguchi
Sahoko
S
Asano
Shogo
S
Nishii
Kazuhiro
K
Nagao
Shizuko
S
Oiso
Yutaka
Y
Itoh
Mitsuyasu
M
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*
D010710:Phosphates; D050608:Sodium-Phosphate Cotransporter Proteins; D001127:Arginine Vasopressin; D051058:Oncogene Protein v-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium