Stimulation of prostacyclin synthesis by thromboxane A2-like prostaglandin endoperoxide analogues in cultured vascular smooth muscle cells.
In this study, the ability of two chemically stable thromboxane A2-like PG endoperoxide analogues, 15S-hydroxy-9 alpha,11 alpha-(epoxymethano)-prosta-5Z,13E-dienoic acid and 15S-hydroxy-11 alpha,9 alpha-(epoxymethano)-prosta-5Z,13E-dienoic acid, to stimulate PGI2 synthesis by cultured vascular smooth muscle cells isolated from rat superior mesenteric arteries was evaluated. The aforementioned analogues, at concentrations of 0.1 to 10 micrograms/ml, stimulated PGI2 synthesis by 1.5 to 3 fold over basal synthesis. Evoked PGI2 synthesis was essentially over within 2 to 3 min of incubation, similar to previous findings made in vascular smooth muscle cells incubated with peptide hormones, vasopressin and angiotensin II. The PG-stimulatory activity of 15S-hydroxy-9 alpha,11 alpha-(epoxymethano)-prosta-5Z-13E-dienoic acid appeared to be receptor-mediated inasmuch as it was completely inhibited by (+/-)5-endo-(6'-carboxyhex-2'Z-enyl)-6-exo-[1''-[N- (phenylthiocarbamoyl)-hydrazono]-ethyl]-bicyclo[2,2,1] heptane, a novel antagonist of PG endoperoxide analogue-provoked smooth muscle contraction and platelet aggregation. The results suggest that thromboxane A2 and/or PG endoperoxide may stimulate PGI2 synthesis in vascular smooth muscle by a direct, receptor-mediated, interaction.
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D011464:Epoprostenol / Q000096:biosynthesis*; D007700:Kinetics; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium
D011450:Prostaglandin Endoperoxides, Synthetic; D014316:Tritium; C028429:U 44069; D015121:6-Ketoprostaglandin F1 alpha; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011464:Epoprostenol