Pasternak G W
Proc Natl Acad Sci U S A. 1980 Jun;77(6):3691-4. doi: 10.1073/pnas.77.6.3691.
The receptor binding of the kappa agonist [3H]ethylketocyclazocine to brain homogenates in vitro and ketocyclazocine (kappa) analgesia in vivo has been investigated and compared to morphine, a mu agonist. Saturation analysis of [3H]ethylketocyclazocine binding in both mice and rats yielded biphasic Scatchard plots similar to those of opiate mu agonists, antagonists, enkephalins, and endorphins. Treatment of brain membranes with monovalent and divalent cation, chelating agents, protein-modifying reagents, and enzymes affected [3H]ethylketocyclazocine binding in a manner similar to that of [3H]morphine. Naloxazone, a long-acting antagonist that selectively abolished high-affinity [3H-DAla2,Met5]enkephalinamide binding in vivo, also selectively blocked high-affinity [3H]ethylketocyclazocine binding. Evaluation of analgesia with writhing and tail-flick assays in animals whose high-affinity binding sites were blocked by naloxazone demonstrated a 6- to 7-fold increase in median effective dose (ED50) values of ketocyclazocine. This decrease in analgesic potency was comparable to morphine's decreased potency in similarly treated mice. These biochemical and pharmacological results suggest that the analgesic properties of both kappa and mu agonists may be mediated through the same subpopulation of receptors, the high-affinity binding sites.
已对κ激动剂[3H]乙基酮环唑新与脑匀浆的体外受体结合以及其在体内的酮环唑新（κ）镇痛作用进行了研究，并与μ激动剂吗啡进行了比较。对小鼠和大鼠的[3H]乙基酮环唑新结合进行饱和分析，得到的双相Scatchard图与阿片类μ激动剂、拮抗剂、脑啡肽和内啡肽的相似。用单价和二价阳离子、螯合剂、蛋白质修饰试剂和酶处理脑膜，对[3H]乙基酮环唑新结合的影响方式与[3H]吗啡相似。纳洛沙宗是一种长效拮抗剂，能在体内选择性消除高亲和力的[3H-DAla2,Met5]脑啡肽酰胺结合，它也能选择性阻断高亲和力的[3H]乙基酮环唑新结合。在用纳洛沙宗阻断高亲和力结合位点的动物中，通过扭体和甩尾试验评估镇痛作用，结果显示酮环唑新的半数有效剂量（ED50）值增加了6至7倍。这种镇痛效力的降低与在同样处理的小鼠中吗啡效力的降低相当。这些生化和药理学结果表明，κ和μ激动剂的镇痛特性可能是通过同一受体亚群，即高亲和力结合位点介导的。
