Uchida M, Imanishi N, Sugasawa T, Morooka S
Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan.
Lipids. 1991 Dec;26(12):1301-4. doi: 10.1007/BF02536553.
The effect of SM-10661, a selective antagonist of platelet-activating factor (PAF), on passive anaphylactic bronchoconstriction was examined in guinea pigs. A challenge of ovalbumin to passively sensitized guinea pigs induced bronchoconstriction, which peaked at 4 min. When SM-10661 was administered intravenously 2 min before ovalbumin challenge, bronchoconstriction was inhibited dose-dependently with an ID50 of 68 mg/kg. In guinea pigs pretreated with 15 micrograms/kg mepyramine which is a suboptimal dose, antigen-induced bronchoconstriction peaked at 4-6 min, but was inhibited by SM-10661 with an ID50 of 21 mg/kg. When guinea pigs were pretreated intravenously with 2.5 mg/kg mepyramine, 1 mg/kg indomethacin and 0.01 mg/kg propranolol, the antigen-induced bronchoconstriction peaked at 6 min. SM-10661 inhibited the response with an ID50 of 45 mg/kg. Histamine- and leukotriene D4-induced bronchoconstrictions were unaffected by up to 100 mg/kg SM-10661. Ovalbumin challenge of minced lungs from passively sensitized guinea pigs triggered the release of leukotrienes and histamine. SM-10661 had no effect on the antigen-induced release of peptide leukotrienes or histamine up to 10(-4) M. These results indicate that SM-10661 may be a useful tool to investigate the role of PAF in antigen-induced anaphylactic bronchoconstriction.
在豚鼠中研究了血小板活化因子（PAF）的选择性拮抗剂SM - 10661对被动过敏性支气管收缩的作用。用卵清蛋白攻击被动致敏的豚鼠会诱发支气管收缩，在4分钟时达到峰值。当在卵清蛋白攻击前2分钟静脉注射SM - 10661时，支气管收缩呈剂量依赖性受到抑制，半数抑制剂量（ID50）为68mg/kg。在用15μg/kg美吡拉敏（次优剂量）预处理的豚鼠中，抗原诱导的支气管收缩在4 - 6分钟时达到峰值，但被SM - 10661抑制，ID50为21mg/kg。当豚鼠静脉注射2.5mg/kg美吡拉敏、1mg/kg吲哚美辛和0.01mg/kg普萘洛尔进行预处理时，抗原诱导的支气管收缩在6分钟时达到峰值。SM - 10661以45mg/kg的ID50抑制该反应。高达100mg/kg的SM - 10661对组胺和白三烯D4诱导的支气管收缩无影响。用被动致敏豚鼠的肺组织匀浆进行卵清蛋白攻击会引发白三烯和组胺的释放。高达10^(-4)M的SM - 10661对抗原诱导的肽白三烯或组胺释放没有影响。这些结果表明，SM - 10661可能是研究PAF在抗原诱导的过敏性支气管收缩中作用的有用工具。
