Effects of cocaine esterase following its repeated administration with cocaine in mice.
Effects of cocaine esterase following its repeated administration with cocaine in mice.
复制标题
可卡因酯酶在小鼠中重复给予可卡因后的影响。
DOI：
10.1016/j.drugalcdep.2009.01.002
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发表时间：
2009-05-01
影响因子：
4.2
通讯作者：
Woods, James H.
中科院分区：
文献类型：
--
作者：
Ko, Mei-Chuan;Narasimhan, Diwahar;Berlin, Aaron A.;Lukacs, Nicholas W.;Sunahara, Roger K.;Woods, James H.
细菌可卡因酯酶（CocE）产生强大的保护和逆转可卡因毒性。本研究的目的是调查CocE与可卡因一起重复给药后的有效性如何变化。通过测量小鼠惊厥发生率和致死率来量化可卡因毒性。采用ELISA法测定CocE的免疫反应。在保护实验中，在腹腔注射致死剂量的可卡因180 mg/kg之前1 min静脉给予CocE 0.3 mg。在补救实验中，在由i. p.可卡因100 mg/kg引起的惊厥发生后1 min，i. v. CocE 0.3 mg。在两种治疗模式中，在相同的动物中进行了4项试验，间隔2周。在前两次试验中，CocE保留了其保护或拯救小鼠的有效性，这些小鼠没有表现出免疫反应。相反，在最后两项试验中，CocE的有效性逐渐降低，伴随着抗CocE抗体滴度的10倍和100倍增加。然而，CocE的有效性可以通过增加CocE的剂量而部分恢复。此外，从重复给药的最低有效剂量逐步增加CocE的剂量也可以更长时间地保持CocE的有效性并减缓抗CocE抗体的产生。这些结果表明，CocE是一种弱抗原，它可以保持其对可卡因毒性的保护和拯救能力。CocE重复使用后的有效性下降可以通过调整CocE治疗的剂量和频率来部分改善。
A bacterial cocaine esterase (CocE) produces robust protection and reversal of cocaine toxicity. The aim of this study was to investigate how effectiveness of CocE was changed following its repeated administration together with cocaine. Cocaine toxicity was quantified by measuring the occurrence of convulsions and lethality in mice. Immunologic responses of CocE were determined using ELISA. In the protection experiment, i.v. CocE 0.3 mg was given 1 min before a lethal dose of i.p. cocaine 180 mg/kg. In the rescue experiment, i.v. CocE 0.3 mg was given 1 min after the occurrence of convulsions elicited by i.p. cocaine 100 mg/kg. In both treatment paradigms, 4 trials were conducted in the same animals with a 2-week interval. CocE retained its effectiveness to protect or rescue mice during the first two trials and these mice did not show an immune response. In contrast, CocE’s effectiveness was gradually reduced in the last two trials, accompanied by 10- and 100-fold increases in the anti-CocE antibody titers. Nevertheless, effectiveness of CocE could be partially recovered by increasing the dose of CocE. In addition, escalating the dose of CocE from the minimum effective dose for repeated administration could also retain CocE’s effectiveness longer and slow the production of anti-CocE antibodies. These results indicate that CocE is a weak antigen and it can maintain its protective and rescuing ability initially against cocaine-induced toxicity. Decreased effectiveness of CocE following repeated use can be partially improved by adjusting the dose and frequency of CocE treatment.
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影响因子：
3.6
作者：
Cooper, Ziva D.;Narasimhan, Diwahar;Woods, James H.
通讯作者：
Woods, James H.
影响因子：
17.7
作者：
Vocci, FJ;Acri, J;Elkashef, A
通讯作者：
Elkashef, A
影响因子：
15.1
作者：
Devlin, Robert J.;Henry, John A.
通讯作者：
Henry, John A.
影响因子：
4.4
作者：
Bresler, MM;Rosser, SJ;Bruce, NC
通讯作者：
Bruce, NC
DOI：
10.1038/nsb742
发表时间：
2002-01-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Larsen, NA;Turner, JM;Wilson, IA
通讯作者：
Wilson, IA