Protection by two ginkgolides, BN-52020 and BN-52021, against guinea-pig lung anaphylaxis.
Interference between the ginkgolides BN-52020 and BN-52021 and the effects of PAF-acether on the cardiovascular and pulmonary functions of guinea-pigs has been studied. BN-52020 (ED50 = 1.1 mg/kg i.v.) and BN-52021 (ED50 = 0.78 mg/kg i.v.) inhibit bronchospasm, hypotension and concomitant generation of TXA2-like activity induced by PAF-acether in anaesthetized guinea-pigs. This protecting activity is specific against PAF-acether since the two ginkgolides do not affect bronchoconstriction, hypotension and TXA2-like activity in the circulating blood due to Histamine, Acetylcholine and LTC4. BN-52021 reduces in a concentration-dependent way the formation of TXB2 caused by PAF-acether in guinea-pig perfused lungs without interference with the effect of Histamine, LTC4 and Arachidonic acid on these tissues. Using actively sensitized (Ovalbumin) guinea-pigs BN-52020 (ED50 = 2.45 mg/kg i.v.) and BN-52021 (ED50 = 1.71 mg/kg i.v.) protect the animals from lethal immunological reaction suggesting that PAF-acether must play a role in the expression of anaphylactic bronchoconstriction and hypotension. The present results indicate that BN-52021 and in a lesser extent BN-52020, which are neither bronchodilators nor cyclooxygenase inhibitors, display a selective antagonistic activity against PAF-acether and may have potential therapeutical implication in asthma.
D000707:Anaphylaxis / Q000517:prevention & control*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D046934:Ginkgolides; D006168:Guinea Pigs; D007783:Lactones; D008168:Lung / Q000187:drug effects*; D008297:Male; D010477:Perfusion; D010936:Plant Extracts / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D013929:Thromboxane B2 / Q000097:blood
D001095:Arachidonic Acids; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010936:Plant Extracts; D010972:Platelet Activating Factor; D016718:Arachidonic Acid; D013929:Thromboxane B2; C045856:ginkgolide B