Nuclear receptor agonists stimulate release of arachidonic acid from rat liver cells.

Release of arachidonic acid (AA) from rat liver cells is stimulated after a 6 h incubation with compounds that are members of the nuclear receptor superfamily, including vitamin D(3), clofibrate, 22(R) OH cholesterol, farnesol, progesterone, testosterone, 17beta-estradiol, hydrocortisone, 3,3'5 triiodothyronine, juvenile hormone III, WY14643, L -thyroxine, the tyrosine analog of thiazolidinediones, GW7845, tamoxifen, hydroxytamoxifen, 17alpha-estradiol and D -thyroxine. Squaline, lanosterol, cholesterol and the 17beta-estradiol antagonist, ICI-182,780, do not stimulate. ICI-182,780 inhibits the release stimulated by 17beta-estradiol, vitamin D(3), 22(R) OH cholesterol, celecoxib or indomethacin. Actinomycin D abolishes the release stimulated by 15-deoxy-delta(12,14) PGJ(2), but is less effective at inhibiting the release stimulated by all of the agonists listed above as well as the release stimulated by 9-cis retinoic acid, all trans -retinoic acid, the thiazidinedione, ciglitazone and the non-steroidal anti-inflammatory drugs, indomethacin and celecoxib. Based on the effects of the 17beta-estradiol antagonist, ICI-182,780, the release of AA appears to be a membrane effect and may not be mediated by the classical estrogen receptors. From the results obtained with actinomycin D, some stimulations may require transcription.