We investigated the possible inhibitory effects of docosahexaenoic acid (DHA) on the contractions induced by U46619 (a TP receptor agonist) and PGF in the isolated coronary and basilar arteries of pig and on the intracellular Ca2+ concentrations elevated by U46619 and PGF in TP or FP receptor-expressing cells. In both coronary and basilar arteries, DHA strongly suppressed U46619- and PGF-induced contractions in a concentration-dependent manner without affecting 80 mM KCl-induced contractions. Particularly, the suppression mediated by DHA vs. U46619-induced contractions suggested a role of competitive antagonism on TP receptor in coronary artery. In coronary artery, DHA did not exert significant inhibitory effects vs. contractions mediated by acetylcholine, histamine, and serotonin. In human TP receptor-expressing cells, DHA almost diminished U46619- and PGF-induced increase in the intracellular Ca2+ concentrations without affecting the increase in PGF-induced Ca2+ concentration in FP receptor-expressing cells. These findings indicate that DHA selectively suppresses the contractions induced by TP receptor agonists in coronary and cerebral arteries partly via competitive antagonism on TP receptors. These actions mediated by DHA seem to partly attribute to its beneficial preventive effects in many cardiovascular diseases