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.