title: Glucocorticoids regulate V1a vasopressin receptor expression by increasing mRNA stability in vascular smooth muscle cells.
abstract: Enhancement of vascular responsiveness is considered to be one of the major contributing factors observed in glucocorticoid-induced hypertension. We examined the effects of glucocorticoids on V1a arginine vasopressin receptor mRNA and protein levels in vascular smooth muscle cells. Dexamethasone (1 mumol/L) produced a 1.8-fold increase in V1a receptor density without changing its affinity. Steady-state values of V1a receptor mRNA, analyzed by Northern blotting, increased 2.7-fold after a 12-hour exposure to dexamethasone. This effect of dexamethasone was blocked by the glucocorticoid antagonist RU38486 and did not occur in the presence of the protein synthesis inhibitor cycloheximide. The V1a receptor gene transcription rate, determined by nuclear run-off assays, was unchanged in cells treated with dexamethasone for 12 hours. Dexamethasone increased the half-life of V1a receptor mRNA by 2.2-fold. These findings suggest that dexamethasone upregulates the expression of the V1a receptor by increasing mRNA stability rather than by gene transcription and that de novo protein synthesis is involved in this regulation.
authors.affiliation: Second Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Murasawa
authors.forename: H
authors.initials: H
authors.lastname: Matsubara
authors.forename: K
authors.initials: K
authors.lastname: Kizima
authors.forename: K
authors.initials: K
authors.lastname: Maruyama
authors.forename: Y
authors.initials: Y
authors.lastname: Mori
authors.forename: M
authors.initials: M
authors.lastname: Inada
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017483:Receptors, Vasopressin / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D012333:RNA, Messenger; D017483:Receptors, Vasopressin; D003907:Dexamethasone