Hashimoto T, Kohno S W, Ohata K, Yanagihara Y, Shida T
Department of Pharmacology, Kyoto Pharmaceutical University, Japan.
Jpn J Pharmacol. 1987 Aug;44(4):447-53. doi: 10.1254/jjp.44.447.
We investigated the influence of butyl 3-(1H-tetrazol-5-yl) oxanilate (MTB) on the release of histamine and slow reacting substance of anaphylaxis (SRS-A) in vitro. MTB dose-dependently inhibited the release of not only histamine but also SRS-A from passively sensitized guinea-pig lung, while disodium cromoglycate (DSCG) hardly affected either release. MTB also resulted in a dose-dependent inhibition of the release of these mediators from the passively sensitized cynomolgus and rhesus monkey and that from human lung at concentrations similar to those inhibiting the release in the guinea-pig. Relatively lower inhibitory activities on the releases of both mediators from the cynomolgus monkey and human lung, but no effects on those from the rhesus monkey were observed with DSCG. MTB dose-dependently inhibited only SRS release from guinea-pig lung induced by phospholipase A2, although the compound did not show any inhibitory activity on the release of those from the calcium ionophore (A23187)-stimulated one. On the other hand, the release of SRS, but not that of histamine from the lung stimulated with A23187 as well as phospholipase A2 was inhibited by N-(3,4-dimethoxycinnamoyl)-anthranilic acid (tranilast, N-5'). From these results, MTB was a potent inhibitor of the anaphylactic release of the mediators, particularly SRS-A. It was suggested that the inhibitory mechanism of MTB is different from those of DSCG and N-5'.
我们研究了3-(1H-四氮唑-5-基)氧杂环庚酯丁酯(MTB)对体外组胺和过敏反应慢反应物质(SRS-A)释放的影响。MTB剂量依赖性地抑制了被动致敏豚鼠肺中组胺和SRS-A的释放，而色甘酸二钠(DSCG)对两者的释放几乎没有影响。MTB还能剂量依赖性地抑制被动致敏食蟹猴、恒河猴以及人肺中这些介质的释放，其浓度与抑制豚鼠释放的浓度相似。DSCG对食蟹猴和人肺中两种介质的释放具有相对较低的抑制活性，但对恒河猴的释放没有影响。MTB仅剂量依赖性地抑制磷脂酶A2诱导的豚鼠肺中SRS的释放，尽管该化合物对钙离子载体(A23187)刺激的释放没有任何抑制活性。另一方面，N-(3,4-二甲氧基肉桂酰基)-邻氨基苯甲酸(曲尼司特，N-5')抑制了A23187和磷脂酶A2刺激的肺中SRS的释放，但不抑制组胺的释放。从这些结果来看，MTB是介质过敏释放的有效抑制剂，尤其是SRS-A。提示MTB的抑制机制与DSCG和N-5'不同。
