title: Effect of VLDL on the inhibition of arachidonic acid transformation by dexamethasone in cultured smooth muscle cells.
abstract: Very-low-density lipoproteins (VLDL) induce a dose-dependent reduction (up to 55%) in the number of specific binding sites and about a 2-fold increase in binding affinity for [3H]dexamethasone in human and rat smooth muscle cells (SMC). Maximal effect of VLDL was achieved within 3-5 h at a lipoprotein concentration 60 micrograms protein/ml. Lipoprotein-mediated reduction in the number of [3H]dexamethasone binding sites resulted in partial loss of cellular sensitivity to hormone action: dexamethasone (1 x 10(-6) M) inhibited the transformation of [14C]arachidonic acid (AA) into metabolites to a lesser extent in SMC preincubated with VLDL (11.5%) than in untreated cells (29.0%). In particular, under these conditions the inhibitory effect of dexamethasone on prostaglandin I2 (PGI2) formation in VLDL-treated SMC was lower than in untreated cells (42.1% vs. 60%). We propose that VLDL is able to counteract the inhibitory effect of glucocorticoids on AA release and PGI2 formation in vascular SMC by reduction of cellular specific glucocorticoid binding sites.
authors.affiliation: Research Centre for Preventive Medicine, Moscow, Russia.
authors.forename: I
authors.initials: I
authors.lastname: Petrichenko
authors.forename: D
authors.initials: D
authors.lastname: Daret
authors.forename: J
authors.initials: J
authors.lastname: Larrue
authors.forename: Y
authors.initials: Y
authors.lastname: Shakhov
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001665:Binding Sites; D002478:Cells, Cultured / Q000187:drug effects; D003907:Dexamethasone / Q000037:antagonists & inhibitors*; D011464:Epoprostenol / Q000378:metabolism; D006801:Humans; D008079:Lipoproteins, VLDL / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D051381:Rats; D014316:Tritium
chemical_list: D008079:Lipoproteins, VLDL; D014316:Tritium; D016718:Arachidonic Acid; D003907:Dexamethasone; D011464:Epoprostenol