Glucocorticoids and dopamine-1 receptors on vascular smooth muscle cells.
The effect of glucocorticoids on the dopamine (DA)-mediated cyclic adenosine monophosphate (cAMP) by intact vascular smooth muscle cells (VSMC) was studied in rats. Cultured VSMC were obtained from renal arteries of 14-week-old Wistar-Kyoto rats by explant method. Micromolar concentrations of dexamethasone (DEX) pretreatment for 48 hours potentiated DA-mediated response without any change of affinity constant. However, micromolar concentrations of aldosterone pretreatment for 48 hours had almost no effect on DA-mediated response. The DEX-induced facilitation began at 6 hours and reached maximum at 24 hours after DEX administration in a dose-dependent manner. Inhibitors of protein and RNA synthesis blocked this glucocorticoid effect. The basal activity of adenylate cyclase in DEX-treated cells was twofold higher than that in control cells. Treatment of VSMC with DEX increased cholera toxin-stimulated and forskolin-stimulated adenylate cyclase activity. However, pertussis toxin treatment did not augment or reduce the effect of DEX treatment. These results suggest that glucocorticoids increase DA-mediated cAMP formation by VSMC through glucocorticoid type II receptors and the induction of protein synthesis and that the activation of the catalytic unit may play some role in this facilitation.
Yasunari
K
K
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Kohno
M
M
Balmforth
A
A
Murakawa
K
K
Yokokawa
K
K
Kurihara
N
N
Takeda
T
T
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000378:metabolism; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D011921:Rats, Inbred WKY; D011954:Receptors, Dopamine / Q000378:metabolism*; D017447:Receptors, Dopamine D1; D012077:Renal Artery / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D013997:Time Factors
D005938:Glucocorticoids; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D003609:Dactinomycin; D012313:RNA; D003907:Dexamethasone; D003513:Cycloheximide; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases