Liu D K, Owens G F
J Toxicol Environ Health. 1987;20(4):379-86. doi: 10.1080/15287398709530991.
The in vivo effects of methylxanthines on 2',5'-oligoadenylate (2,5An) synthetase activity, an interferon-inducible enzyme, were investigated in rat liver nuclei. Caffeine given at 50 mg/kg ip or theobromine given at 80 mg/kg sc twice daily for 5 d resulted in a 60% reduction (p less than 0.01 and p less than 0.05, respectively) of 2,5An synthetase activity in liver nuclei. Theophylline given at 80 mg/kg sc by the same regimen reduced the enzyme activity by 42% (p less than 0.05). Nuclear 2'-phosphodiesterase activity, which catalyzes the degradation of 2,5An, remained low and unchanged following the drug treatments. When animals receiving caffeine were also given the interferon inducer poly(I)poly(C) at 500 micrograms/kg ip once daily for the last 2 d of caffeine treatment, it resulted in the same fourfold increase in 2,5An synthetase activity as shown with poly(I)poly(C) alone. These results suggest that methylxanthines may interact with interferon-mediated actions. The reason for the inhibitory effect of methylxanthines on the basal but not on the induced 2,5An synthetase remains to be investigated.
在大鼠肝细胞核中研究了甲基黄嘌呤对2',5'-寡腺苷酸（2,5An）合成酶活性的体内效应，该酶是一种干扰素诱导酶。以50mg/kg腹腔注射给予咖啡因或80mg/kg皮下注射给予可可碱，每日两次，连续5天，导致肝细胞核中2,5An合成酶活性分别降低60%（p<0.01和p<0.05）。以相同方案80mg/kg皮下注射给予茶碱使酶活性降低42%（p<0.05）。催化2,5An降解的核2'-磷酸二酯酶活性在药物处理后保持较低且未改变。在咖啡因处理的最后2天，当接受咖啡因的动物还以500μg/kg腹腔注射给予干扰素诱导剂聚肌苷酸-聚胞苷酸（poly(I)poly(C)）时，其导致2,5An合成酶活性增加四倍，与单独使用poly(I)poly(C)时相同。这些结果表明甲基黄嘌呤可能与干扰素介导的作用相互作用。甲基黄嘌呤对基础状态而非诱导状态的2,5An合成酶产生抑制作用的原因仍有待研究。
