Effects of OKY 1581 on bronchoconstrictor responses to arachidonic acid and PGH2.
The influence of OKY 1581, a thromboxane synthase inhibitor, on airway responses to arachidonic acid and endoperoxide, [prostaglandin (PG) H2], were investigated in anesthetized, paralyzed, mechanically ventilated cats. Intravenous injections of arachidonic acid and PGH2 caused dose-related increases in transpulmonary pressure and lung resistance and decreases in dynamic and static compliance. OKY 1581 significantly decreased airway responses to arachidonic acid but not to PGH2. Sodium meclofenamate, a cyclooxygenase inhibitor, abolished airway responses to arachidonic acid but had no effect on airway responses to PGH2. OKY 1581 or meclofenamate has no effect on airway responses to PGF2 alpha, PGD2, or U 46619, a thromboxane mimic. In microsomal fractions from the lung, OKY 1581 inhibited thromboxane formation without decreasing prostacyclin synthesis or cyclooxygenase activity. These studies show that OKY 1581 is a selective thromboxane synthesis inhibitor in the cat lung and suggest that a substantial part of the bronchoconstrictor response to arachidonic acid is due to thromboxane A2 formation. Moreover, the present data suggest that airway responses to endogenously released and exogenous PGH2 are mediated differently and that a significant part of the response to exogenous PGH2 may be due to activation of an endoperoxide/thromboxane receptor, since responses to PGH2 are blocked by the thromboxane receptor antagonist SQ 29548.
D000179:Acrylates / Q000494:pharmacology*; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D002415:Cats; D015237:Dinoprost; D008689:Methacrylates / Q000494:pharmacology*; D015230:Prostaglandin D2; D011449:Prostaglandin Endoperoxides / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D044262:Prostaglandin H2; D011457:Prostaglandins D / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D011463:Prostaglandins H / Q000494:pharmacology*; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000502:physiology; D017482:Receptors, Thromboxane; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D000179:Acrylates; D001095:Arachidonic Acids; D008689:Methacrylates; D011449:Prostaglandin Endoperoxides; D011450:Prostaglandin Endoperoxides, Synthetic; D011457:Prostaglandins D; D011460:Prostaglandins F; D011463:Prostaglandins H; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D016718:Arachidonic Acid; D044262:Prostaglandin H2; C031517:2-methyl-3-(4-(3-pyridinylmethyl)phenyl)-2-propenoic acid; D015237:Dinoprost; D013930:Thromboxane-A Synthase; D015230:Prostaglandin D2