Effect of thromboxane synthetase inhibitors (OKY-046, OKY-1580) on the action of bronchoactive agents in guinea pig tracheal strips and on arachidonate metabolism in guinea pig lung lobes.
We investigated the effect of the thromboxane synthetase inhibitors, OKY-046 and OKY-1580, on the action of bronchoactive agents in guinea pig tracheal strips, and on arachidonic acid metabolism in isolated perfused guinea pig lung lobes. OKY-046 and OKY-1580 attenuated histamine-, serotonin-, acetylcholine-, bradykinin- and prostaglandin F2- induced contractile responses in guinea pig tracheal strips dose-dependently and potentiated isoproterenol-, salbutamol- and prostaglandin E2-induced relaxation in guinea pig tracheal strips dose-dependently. In addition, OKY-046 and OKY-1580 inhibited the biosynthesis of thromboxane A2 and accelerated the production of 6-keto prostaglandin F1 from arachidonic acid in isolated perfused guinea pig lung lobes. The above results suggest that OKY-046 and OKY-1580 might be useful therapeutic agents for the treatment of pulmonary thromboembolism and chronic obstructive lung diseases.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001993:Bronchodilator Agents / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014132:Trachea / Q000187:drug effects*
D001095:Arachidonic Acids; D001993:Bronchodilator Agents; D008689:Methacrylates; D016718:Arachidonic Acid; C031517:2-methyl-3-(4-(3-pyridinylmethyl)phenyl)-2-propenoic acid; D006632:Histamine; D010088:Oxidoreductases; D013930:Thromboxane-A Synthase; C034364:ozagrel