Maloteaux J M, Octave J N, Laterre E C, Laduron P M
Laboratoire de Neurochimie, Université Catholique de Louvain, Brussels, Belgium.
Naunyn Schmiedebergs Arch Pharmacol. 1989 Jan-Feb;339(1-2):192-9. doi: 10.1007/BF00165143.
There was stereospecific binding of 3H-lofentanil (KD value = 1.53 nM) to membranes of neuroblastoma-glioma NG 108-15 cells which are known to bear high affinity binding sites for enkephalin derivatives (delta-opiate receptor subtype). There was no high affinity specific binding of the mu-opiate specific ligand 3H-sufentanil. The specific binding of 3H-lofentanil to delta-opiate receptor subtype was down-regulated (decrease in Bmax value without change in the KD value) after prolonged incubation of the cells in the presence of leu- and met- enkephalin (0.1 microM). There was no down-regulation of the opiate receptors (3H-lofentanil and 3H-D-ala-D-leu-enkephalin specific binding) after incubation of NG 108-15 cells with drugs from the fentanyl series (alfentanil or sufentanil). In cultured neurones from rat forebrain (15 day old embryos), the 3H-lofentanil binding was specific with high affinity (KD: 0.048 nM) and a slow dissociation rate similar to that in adult rat cortex. Drugs of the fentanyl series (4-anilino-piperidines) were potent displacers whereas agonists of the delta- (enkephalin derivatives), sigma- (phencyclidine, haloperidol, 3-hydroxyphenyl-propylpiperidine) or K- (U 50488) opiate sites had a low affinity (Ki greater than 0.5 microM) for 3H-lofentanil specific binding sites. Since there was also specific binding of 3H-sufentanil, the opiate receptors in cultured neurones seem to be mainly of the mu-subtype and this is consistent with the ontogeny of opiate receptors subtypes. These receptors were down-regulated after incubation in the presence of etorphine, sufentanil and alfentanil but not enkephalin derivatives.(ABSTRACT TRUNCATED AT 250 WORDS)
3H-洛芬太尼（KD值 = 1.53 nM）与神经母细胞瘤-胶质瘤NG 108-15细胞的膜存在立体特异性结合，已知该细胞对脑啡肽衍生物（δ-阿片受体亚型）具有高亲和力结合位点。μ-阿片特异性配体3H-舒芬太尼不存在高亲和力特异性结合。在亮氨酸脑啡肽和甲硫氨酸脑啡肽（0.1 microM）存在下，将细胞长时间孵育后，3H-洛芬太尼与δ-阿片受体亚型的特异性结合被下调（Bmax值降低，KD值不变）。用芬太尼系列药物（阿芬太尼或舒芬太尼）孵育NG 108-15细胞后，阿片受体（3H-洛芬太尼和3H-D-丙氨酸-D-亮氨酸脑啡肽特异性结合）未被下调。在大鼠前脑（15日龄胚胎）的培养神经元中，3H-洛芬太尼结合具有特异性，亲和力高（KD：0.048 nM），解离速率缓慢，类似于成年大鼠皮层。芬太尼系列药物（4-苯胺基哌啶）是强效置换剂，而δ-（脑啡肽衍生物）、σ-（苯环己哌啶、氟哌啶醇、3-羟基苯基丙基哌啶）或κ-（U 50488）阿片位点的激动剂对3H-洛芬太尼特异性结合位点的亲和力较低（Ki大于0.5 microM）。由于也存在3H-舒芬太尼的特异性结合，培养神经元中的阿片受体似乎主要是μ-亚型，这与阿片受体亚型的个体发生一致。在埃托啡、舒芬太尼和阿芬太尼存在下孵育后，这些受体被下调，但脑啡肽衍生物不存在此现象。（摘要截短于250字）
