Effect of glucocorticoid on prostaglandin E1 mediated cyclic AMP formation by vascular smooth muscle cells.
The effect of glucocorticoid on the prostaglandin E1 (PGE1)-mediated cyclic AMP (cAMP) formation by vascular smooth muscle cells (VSMC) from renal arteries (RA) was studied in rats. Dexamethasone (DEX) at concentrations ranging from 10(-10) to approximately 10(-8) mol/l dose-dependently potentiates the PGE1-mediated response. This facilitation began at 6 h and reached its maximum after 24 h of DEX administration. Aldosterone (10(-6) mol/l) did not affect the dose-response curve of PGE1. Inhibitors of protein and RNA synthesis blocked this glucocorticoid effect. The basal activity of adenylate cyclase in DEX-treated cells was twice as high as in control cells. Treatment of VSMC with DEX increased cholera toxin- and pertussis toxin-stimulated adenylate cyclase activity. DEX treatment also augments forskolin-stimulated adenylate cyclase activity. These results suggest that DEX increases PGE1-mediated cAMP formation of VSMC from RA through a mechanism that involves the induction of protein synthesis, and that the activation of the catalytic unit may play some role in this facilitating process.
Yasunari
K
K
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Kohno
M
M
Murakawa
K
K
Yokokawa
K
K
Takeda
T
T
D000527:Alprostadil / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis*; D003907:Dexamethasone / Q000494:pharmacology*; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D051381:Rats; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000378:metabolism*; D018078:Receptors, Prostaglandin E; D012077:Renal Artery / Q000378:metabolism
D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D003907:Dexamethasone; D000242:Cyclic AMP; D000527:Alprostadil