Pons F, Touvay C, Lejeune V, Carré C, Vilain B, Broquet C, Mencia-Huerta J M, Braquet P
Institut Henri Beaufour, Les Ulis, France.
J Lipid Mediat. 1989 Nov-Dec;1(6):329-40.
Intravenous injection of BN 52021 in anesthetized guinea-pigs, 5 min before challenge, inhibited in a dose-dependent fashion with an IC50 of 0.90 mg/kg the bronchoconstriction induced by PAF (60 ng/kg i.v.). However, BN 52021 did not prevent the leukopenia following PAF injection but significantly inhibited the thrombocytopenia induced by PAF. The dioxolan compound, BN 52111, dose-dependently reduced the bronchoconstriction (IC50 = 0.27 mg/kg) and at doses higher than 1 mg/kg partially antagonized the decrease in the number of circulating platelets and leukocytes induced by PAF. BN 52115 also markedly inhibited the bronchoconstriction (IC50 = 0.36 mg/kg) as well as the thrombocytopenia induced by PAF, but was without significant effect on the leukopenia. These results demonstrate that the two dioxolan compounds, BN 52111 and BN 52115, are more potent than BN 52021 in inhibiting the in vivo bronchopulmonary alterations induced by PAF. Since these alterations are related to the activation of platelets by the autacoid, these blood elements are probably the targets of BN 52111 and BN 52115. Injection of PAF (10 and 100 ng) via the pulmonary artery of ventilated and perfused guinea-pig lungs induced dose-dependent increases in pulmonary inflation pressure (PIP) and pulmonary perfusion pressure (PPP), associated with a dose-dependent release of thromboxane B2 (TxB2). Addition of BN 52021, BN 52111 or BN 52115 (0.1, 1 or 10 microM) to the perfusion medium, 15 min before challenge, dose-dependently inhibited the bronchopulmonary effects of PAF. Although BN 52111 was the more potent in inhibiting the PAF-induced increase in PIP, BN 52021 was the more active with respect to the PAF-evoked generation of TxB2, suggesting that the two phenomena are not directly related.
在麻醉的豚鼠中，于激发前5分钟静脉注射BN 52021，能以剂量依赖方式抑制由PAF（60 ng/kg静脉注射）诱导的支气管收缩，IC50为0.90 mg/kg。然而，BN 52021不能预防PAF注射后的白细胞减少，但能显著抑制PAF诱导的血小板减少。二氧戊环化合物BN 52111能剂量依赖性地减轻支气管收缩（IC50 = 0.27 mg/kg），且在高于1 mg/kg的剂量时能部分拮抗PAF诱导的循环血小板和白细胞数量的减少。BN 52115也能显著抑制支气管收缩（IC50 = 0.36 mg/kg）以及PAF诱导的血小板减少，但对白细胞减少无显著影响。这些结果表明，两种二氧戊环化合物BN 52111和BN 52115在抑制PAF诱导的体内支气管肺改变方面比BN 52021更有效。由于这些改变与自分泌物质激活血小板有关，这些血液成分可能是BN 52111和BN 52115的作用靶点。通过通气和灌注的豚鼠肺的肺动脉注射PAF（10和100 ng）会导致肺充气压力（PIP）和肺灌注压力（PPP）呈剂量依赖性增加，并伴有血栓素B2（TxB2）的剂量依赖性释放。在激发前15分钟向灌注介质中添加BN 52021、BN 52111或BN 52115（0.1、1或10 microM），能剂量依赖性地抑制PAF的支气管肺效应。尽管BN 52111在抑制PAF诱导的PIP增加方面更有效，但BN 52021在抑制PAF诱发的TxB2生成方面更活跃，这表明这两种现象并非直接相关。
