High affinity binding of [3H] cocaine to rat liver microsomes.
High affinity binding of [3H] cocaine to rat liver microsomes.
复制标题
[3H]可卡因与大鼠肝微粒体的高亲和力结合。
DOI：
10.1016/0024-3205(88)90447-x
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发表时间：
1988
期刊：
影响因子：
6.1
通讯作者：
Eldefrawi,ME
中科院分区：
文献类型：
--
作者：
el-Maghrabi,EA;Calligaro,DO;Eldefrawi,ME
摘要 [3 H]可卡因与大鼠肝微粒体可逆结合，具有高亲和力 (K D 2.3±1.1. nM) 和立体特异性。在溶酶体、线粒体和核部分中检测到很少的结合。结合动力学很慢（缔合 T 1 2 6 分钟，解离 17 分钟），动力学计算的 K D 为 2 nM。苯巴比妥诱导混合功能氧化酶并未对[3H]可卡因结合产生显着变化。另一方面，长期服用可卡因会显着减少[3H]可卡因结合。两种治疗均不影响肝脏结合蛋白对可卡因的亲和力。与来自大鼠肝脏的微粒体相比，来自小鼠和人类肝脏的微粒体具有较少的可卡因结合蛋白和较低的可卡因亲和力。 [3H]可卡因与大鼠肝微粒体的结合对单价阳离子不敏感，并且对生物胺的敏感性比大鼠纹状体中的可卡因受体低10倍以上。然而，肝脏蛋白对除去甲可卡因外的可卡因和代谢物具有较高的亲和力。胺摄取抑制剂取代与肝脏结合的[ 3 H]可卡因，其效力等级顺序与它们取代与纹状体结合的[ 3 H]可卡因不同。肝脏中的这种高亲和力 [3 H] 可卡因结合蛋白不太可能是单加氧酶，但可能在可卡因诱导的肝毒性中发挥作用。
Abstract [3 H] Cocaine bound reversibly, with high affinity (K D 2.3±1.1. nM) and stereospecificity to rat liver microsomes. Little binding was detected in the lysosomal, mitochondrial and nuclear fractions. The binding kinetics were slow (T 1 2 for association, 6 min and for dissociation 17 min), and the kinetically calculated K D was 2 nM. Induction of mixed function oxidases by phenobarbital did not produce significant change in [3 H] cocaine binding. On the other hand, chronic administration of cocaine reduced [3 H] cocaine binding drastically. Neither treatment affected the affinity of the liver binding protein for cocaine. Microsomes from mouse and human livers had less cocaine-binding protein and lower affinity for cocaine than those from rat liver. Binding of [3 H] cocaine for rat liver microsomes was insensitive to monovalent cations and> 10 fold less sensitive to biogenic amines than the cocaine receptor in rat striatum. However, the liver protein had higher affinity for cocaine and metabolites except for norcocaine. Amine uptake inhibitors displaced [3 H] cocaine binding to liver with a different rank order of potency than their displacement of [3 H] cocaine binding to striatum. This high affinity [3 H] cocaine binding protein in liver is not likely to be a monooxygenase, but may have a role in cocaine-induced hepatotoxicity.