Schoffelmeer A N, De Vries T J, Hogenboom F, Hruby V J, Portoghese P S, Mulder A H
Department of Pharmacology, Free University, Medical Faculty, Amsterdam, The Netherlands.
J Pharmacol Exp Ther. 1992 Oct;263(1):20-4.
The present study addressed the question as to whether or not' interacting mu and delta opioid receptors, which may constitute an opioid receptor complex-inhibitory coupled to adenylate cyclase in rat neostriatum, display different antagonistic properties than the classical (noncomplexed) mu and delta receptors. In concentrations that antagonized the presynaptic inhibitory effect of [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAMGO) on [3H]norepinephrine release from rat neocortical slices, the cyclic somatostatin-related mu opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 did not affect the inhibition of dopamine-sensitive adenylate cyclase caused by DAMGO in neostriatal slices. The delta opioid receptor antagonist naltrindole appeared to be about 200-fold more effective as an antagonist against inhibitory effect of [D-Ser2(O-tert-butyl),Leu5]enkephalyl-Thr6 on [14C]acetylcholine release from neostriatal slices than against the inhibitory effect of DAMGO on [3H]norepinephrine release from neocortical slices, in agreement with the involvement of presynaptic delta and mu receptors, respectively. However, regarding the inhibitory effect of DAMGO and [D-Ser2(O-tert-butyl),Leu5] enkephalyl-Thr6 on adenylate cyclase activity in neostriatal slices, naltrindole not only displayed a very low affinity but also only 10-fold delta-selectivity. In striking contrast to D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 and naltrindole, naloxone did not discriminate between the neurotransmitter release-and adenylate cyclase-inhibitory effects of DAMGO and [D-Ser2(O-tert-butyl), Leu5]enkephalyl-Thr6.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究探讨了相互作用的μ和δ阿片受体（可能构成一种与大鼠新纹状体中腺苷酸环化酶偶联的阿片受体复合物）是否比经典的（非复合的）μ和δ受体表现出不同的拮抗特性这一问题。在拮抗[D - Ala2，MePhe4，Gly - ol5]脑啡肽（DAMGO）对大鼠新皮质切片中[3H]去甲肾上腺素释放的突触前抑制作用的浓度下，环状生长抑素相关的μ阿片受体拮抗剂D - Phe - Cys - Tyr - D - Trp - Orn - Thr - Pen - Thr - NH2并不影响DAMGO对新纹状体切片中多巴胺敏感的腺苷酸环化酶的抑制作用。δ阿片受体拮抗剂纳曲吲哚作为拮抗剂，对[D - Ser2（O - 叔丁基），Leu5]脑啡肽 - Thr6对新纹状体切片中[14C]乙酰胆碱释放的抑制作用的拮抗效果似乎比对DAMGO对新皮质切片中[3H]去甲肾上腺素释放的抑制作用的拮抗效果强约200倍，这分别与突触前δ和μ受体的参与情况一致。然而，就DAMGO和[D - Ser2（O - 叔丁基），Leu5]脑啡肽 - Thr6对新纹状体切片中腺苷酸环化酶活性的抑制作用而言，纳曲吲哚不仅表现出非常低的亲和力，而且仅具有10倍的δ选择性。与D - Phe - Cys - Tyr - D - Trp - Orn - Thr - Pen - Thr - NH2和纳曲吲哚形成鲜明对比的是，纳洛酮无法区分DAMGO和[D - Ser2（O - 叔丁基），Leu5]脑啡肽 - Thr6对神经递质释放和腺苷酸环化酶的抑制作用。（摘要截于250字）
