title: Proadifen-induced production of prostacyclin by equine peritoneal macrophages.
abstract: A study was performed to determine the effect of proadifen hydrochloride on prostacyclin (prostaglandin I2 [PGI2]) and thromboxane A2 (TxA2) synthesis by equine peritoneal macrophages and the effect of proadifen on endotoxin-induced synthesis of PGI2 and TxA2 by equine macrophages. Peritoneal macrophages (2.5 x 10(6)/ml) were incubated for 6 hours in tissue culture media containing 1) nothing (nontreated control), 2) proadifen hydrochloride (20, 100, 250, and 500 mumol/L, 3) endotoxin (5 ng/ml), or 4) the calcium ionophore A23187 (0.95 mumol/L). In a second series of experiments, peritoneal macrophages were incubated with endotoxin (5 ng/ml) and proadifen (250 umol/L), for 6 hours. Concentrations of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2, the stable metabolites of PGI2 and TxA2, were determined in the incubation media by radioimmunoassay. Proadifen caused increased synthesis of PGI2 by equine macrophages, without affecting TxA2 production. The increased PGI2 production was similar to that induced by endotoxin and calcium ionophore; however, the latter 2 agents significantly stimulated TxA2 production as well (P less than 0.05). There were no significant differences among mean concentrations of 6-keto-PGF1 alpha in media from macrophages treated with 100, 250, or 500 mumol/L proadifen, but there was a significant curvilinear regression between their concentrations. The ratio of thromboxane B2 to 6-keto-PGF1 alpha was significantly lower than baseline in incubation media from macrophages exposed to proadifen, endotoxin, and calcium ionophore. Proadifen hydrochloride did not significantly change equine peritoneal macrophage production of PGI2 or TxA2 in response to endotoxin.
authors.affiliation: Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens 30602.
authors.forename: D D
authors.initials: DD
authors.lastname: Morris
authors.forename: J N
authors.initials: JN
authors.lastname: Moore
authors.forename: N
authors.initials: N
authors.lastname: Wiltshire
authors.forename: K
authors.initials: K
authors.lastname: Fischer
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D006736:Horses / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D010537:Peritoneum / Q000166:cytology; D011335:Proadifen / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000096:biosynthesis
chemical_list: D004731:Endotoxins; D000001:Calcimycin; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D011335:Proadifen; D011464:Epoprostenol