Frances B, Moisand C, Meunier J C
Eur J Pharmacol. 1985 Nov 5;117(2):223-32. doi: 10.1016/0014-2999(85)90607-7.
Rabbit and guinea-pig cerebellum membrane preparations contain a high proportion (greater than 80%) of mu- and of kappa-opioid binding sites, respectively. These preparations were therefore used to compare the regulation of binding of mu- and of kappa-opioid agonists and antagonists by sodium ions and by guanyl-5'-yl imidodiphosphate. We report here that Na+ ions, Gpp(NH)p and most efficiently, the two agents in association selectively inhibited binding of opioid agonists not only in the mu preparation (rabbit cerebellum) but also in the kappa preparation (guinea-pig cerebellum). These allosteric effectors did not inhibit equilibrium binding of antagonists (naloxone, Mr 2266 or diprenorphine) in the two preparations. Taken together these results suggest that occupancy either of the mu-receptor by a mu-agonist or of the kappa-receptor by a kappa-agonist may be accompanied by similar if not identical molecular events. They also suggest a method to rapidly screen newly designed drugs as mu- or kappa-opioid agonists or antagonists.
兔和豚鼠小脑膜制剂分别含有高比例（大于80%）的μ-和κ-阿片样物质结合位点。因此，这些制剂被用于比较钠离子和5'-鸟苷酰亚胺二磷酸对μ-和κ-阿片样物质激动剂及拮抗剂结合的调节作用。我们在此报告，钠离子、Gpp(NH)p，最有效的是这两种试剂联合使用，不仅在μ制剂（兔小脑）中，而且在κ制剂（豚鼠小脑）中，都能选择性地抑制阿片样物质激动剂的结合。这些变构效应剂在这两种制剂中并不抑制拮抗剂（纳洛酮、分子量2266或二丙诺啡）的平衡结合。综合这些结果表明，μ-激动剂占据μ-受体或κ-激动剂占据κ-受体可能伴随着相似（如果不是相同）的分子事件。它们还提示了一种快速筛选新设计的作为μ-或κ-阿片样物质激动剂或拮抗剂的药物的方法。
