Su T P
J Pharmacol Exp Ther. 1982 Nov;223(2):284-90.
A portion of the specific binding of tritiated SKF-10047 to the guinea-pig brain suspension of the particulate fraction is not inhibited by the strong narcotic analgesic l-etorphine. The binding properties of these etorphine-inaccessible (EI) sites were examined. The specific binding of [3H]SKF-10047 to the EI sites is saturable. Scatchard analysis of the saturation curve revealed a single class of binding sites with apparent Kd of 252 nM and an estimated Bmax of 663 fmol/mg of protein. The EI binding was reduced by heat treatment, trypsin digestion and phospholipase C digestion. The presence of sodium ions slightly increased specific EI binding. Lithium ion increased the EI binding by about 38% at the optimal concentration of 1 mM. Divalent cations such as Mg++, Ca++ and Mn++ reduced EI binding. Morphine-like drugs such as morphine, levorphanol and naltrexone were poor inhibitors for the EI binding, whereas opioid derivatives such as pentazocine, dextrallorphan, cyclazocine, SKF-10047 and dextrorphan were potent inhibitors. Nonopioid drugs such as haloperidol, imipramine, pimozide and propranolol were also potent inhibitors of the EI binding. Distribution of the EI sites in brain was different from that of the mu receptor: highest concentration of EI sites was found in brainstem, midbrain and cerebellum, whereas lower concentrations were found in striatum and cortex. It is suggested that EI sites are not mu receptors but may represent sigma receptors in the central nervous system, mediating psychotomimetic effects of several opioids and other drugs.
氚标记的SKF - 10047与豚鼠脑微粒体部分悬浮液的特异性结合，有一部分不受强效麻醉性镇痛药左啡诺抑制。对这些左啡诺不可及（EI）位点的结合特性进行了研究。[3H]SKF - 10047与EI位点的特异性结合是可饱和的。对饱和曲线进行Scatchard分析，发现有一类结合位点，其表观解离常数（Kd）为252 nM，每毫克蛋白质的最大结合量（Bmax）估计为663 fmol。热处理、胰蛋白酶消化和磷脂酶C消化可降低EI结合。钠离子的存在可使特异性EI结合略有增加。锂离子在最佳浓度1 mM时可使EI结合增加约38%。二价阳离子如Mg++、Ca++和Mn++可降低EI结合。吗啡、左啡诺和纳曲酮等类吗啡药物对EI结合的抑制作用较弱，而喷他佐辛、右丙氧芬、环唑辛、SKF - 10047和右啡烷等阿片类衍生物是强效抑制剂。氟哌啶醇、丙咪嗪、匹莫齐特和普萘洛尔等非阿片类药物也是EI结合的强效抑制剂。EI位点在脑中的分布与μ受体不同：EI位点在脑干、中脑和小脑中浓度最高，而在纹状体和皮质中浓度较低。提示EI位点不是μ受体，可能代表中枢神经系统中的σ受体，介导几种阿片类药物和其他药物的拟精神病效应。
