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用10-羧甲基-9-吖啶酮处理后小鼠体内环磷酸腺苷代谢与干扰素诱导

Cyclic AMP metabolism and interferon induction in mice after treatment with 10-carboxymethyl-9-acridanone.

作者信息

Römer W, Tonew E, Schulze W

出版信息

Acta Virol. 1986 Sep;30(5):411-7.

PMID:2431609
Abstract

The low molecular weight substance 10-carboxymethyl-9-acridanone (CMA) is capable to induce interferon (IFN) production. In order to determine the effect of CMA on cyclic AMP alterations in relation to IFN production, male ABD2F1 hybrid mice were orally treated with several concentrations of CMA (400, 600 and 800 mg/kg) for varying periods of time up to 24 hr. IFN titres were detected as early as 3 and 4 hr, respectively, in mouse plasma after CMA administration, and their production continued for at least 24 hr. Maximum IFN titres were assayed in the presence of 800 mg/kg (3,200 IU/ml) CMA. Measuring of the intracellular concentrations of cyclic AMP in thymus and spleen revealed that in early stage (0.5 to 2 hr) CMA exhibited a dose dependent increase. The drug acted as an inhibitor of low Km cAMP phosphodiesterase in cell homogenates; a significantly enhanced enzyme activity (1 to 4 hr) was found after exposure to CMA in vivo.

摘要

低分子量物质10-羧甲基-9-吖啶酮(CMA)能够诱导干扰素(IFN)的产生。为了确定CMA对与IFN产生相关的环磷酸腺苷(cAMP)变化的影响,将雄性ABD2F1杂交小鼠口服给予几种浓度的CMA(400、600和800mg/kg),持续不同时间段直至24小时。在给予CMA后,分别早在3小时和4小时在小鼠血浆中检测到IFN滴度,并且其产生持续至少24小时。在800mg/kg(3200IU/ml)CMA存在下测定到最大IFN滴度。对胸腺和脾脏中cAMP的细胞内浓度进行测量发现,在早期阶段(0.5至2小时),CMA呈现出剂量依赖性增加。该药物在细胞匀浆中作为低Km cAMP磷酸二酯酶的抑制剂;在体内暴露于CMA后发现酶活性显著增强(1至4小时)。

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