Shibata H, Minami E, Hirata R, Mizutani N, Nabe T, Kohno S
Central Research Laboratory, Kotaro Pharmaceutical Co. Ltd., Takatsuki, Osaka, Japan.
Inflamm Res. 2000 Oct;49(10):553-9. doi: 10.1007/s000110050631.
We previously reported that oral l-ephedrine showed extraordinarily rapid inhibition of 48-h passive cutaneous anaphylaxis (PCA) in rats. In the present study, in vivo and in vitro experiments were performed to elucidate a possible mechanism for the inhibition.
Rat antiserum was prepared with dinitrophenylated Ascaris suum extract + Bordetella pertussis.
Wistar rats were passively skin-sensitised, actively sensitised or non-sensitised. l-Ephedrine immediately before provocations was orally or intravenously administered in in vivo experiments. In in vitro experiments, the drug was added at various time and concentrations before the challenge.
The intensity of PCA was assessed by dye leakage method. Histamine and serotonin released in vitro or retained in the skin in vivo by anaphylaxis were assayed fluorometrically.
Oral l-ephedrine rapidly inhibited the PCA by inhibiting the release of histamine and serotonin from the reaction site, whereas anaphylactic histamine and serotonin releases from skin fragments were not affected by the drug. Furthermore, the orally administered drug influenced neither the histamine- nor serotonin-induced cutaneous vascular permeability.
These results were strongly indicative that the prompt suppression of the PCA by oral l-ephedrine was not exerted following the drug was absorbed from the gastrointestinal tract. Thus, the result may be from an indirect inhibition of chemical mediator release, possibly through an unidentified stimulation of the nervous system, but not from the inhibition of chemical mediator release by the direct interaction of drug to mast cells and not from the decreased vascular permeability.
我们之前报道过口服l - 麻黄碱对大鼠48小时被动皮肤过敏反应(PCA)具有异常快速的抑制作用。在本研究中,进行了体内和体外实验以阐明这种抑制作用的可能机制。
用二硝基苯基化猪蛔虫提取物 + 百日咳博德特氏菌制备大鼠抗血清。
将Wistar大鼠进行被动皮肤致敏、主动致敏或未致敏处理。在体内实验中,在激发前立即口服或静脉注射l - 麻黄碱。在体外实验中,在激发前不同时间以不同浓度加入该药物。
通过染料渗漏法评估PCA的强度。用荧光法测定过敏反应在体外释放或在体内皮肤中保留的组胺和5 - 羟色胺。
口服l - 麻黄碱通过抑制组胺和5 - 羟色胺从反应部位的释放而迅速抑制PCA,而皮肤碎片中过敏反应性组胺和5 - 羟色胺的释放不受该药物影响。此外,口服该药物对组胺或5 - 羟色胺诱导的皮肤血管通透性均无影响。
这些结果强烈表明口服l - 麻黄碱对PCA的迅速抑制作用并非在药物从胃肠道吸收后发挥。因此,该结果可能源于对化学介质释放的间接抑制,可能是通过对神经系统的未知刺激,而不是源于药物与肥大细胞直接相互作用对化学介质释放的抑制,也不是源于血管通透性的降低。