Shahabi N A, Burtness M Z, Sharp B M
Department of Medicine, Hennepin County Medical Center, Minneapolis, MN.
Biochem Biophys Res Commun. 1991 Mar 29;175(3):936-42. doi: 10.1016/0006-291x(91)91655-v.
High affinity binding sites for beta-endorphin1-31 (beta-EP) have been observed on transformed mononuclear cells such as the human U937 monocyte-like cell line and the murine EL4-thymoma line, and on normal murine splenocytes. Binding of beta-EP at these sites is resistant to competition by naloxone and other opiate receptor ligands but sensitive to N-acetyl-beta-endorphin1-31 (N-Ac), cations and GTP-gamma-sulfate. Thus, the following studies were done to determine the functional significance of binding beta-EP and N-Ac. beta-EP suppressed phytohemagglutinin (PHA)-stimulated [3H]thymidine uptake in a dose-dependent, naloxone-insensitive fashion. beta-Endorphin1-27, (des)-tyrosine beta-endorphin2-31, or N-Ac failed to duplicate the suppressive effect of beta-EP. However, N-Ac, which is equipotent to beta-EP at displacing 125I-beta-EP bound to murine splenocytes or U937 cells, antagonized the suppressive effect of beta-EP. Taken together with previous binding studies, the present observations suggest that beta-EP effects receptor-mediated responses on normal immunocytes that do not depend on the activation of neuronal-like opiate receptors which are naloxone-sensitive. N-Ac, which shows minimal binding to such brain opiate receptors, is a potent functional antagonist of the naloxone-insensitive immunocyte receptor for beta-EP.
在转化的单核细胞（如人U937单核细胞样细胞系和鼠EL4胸腺瘤细胞系）以及正常鼠脾细胞上已观察到β-内啡肽1-31（β-EP）的高亲和力结合位点。β-EP在这些位点的结合对纳洛酮和其他阿片受体配体的竞争具有抗性，但对N-乙酰-β-内啡肽1-31（N-Ac）、阳离子和鸟苷-γ-硫酸敏感。因此，进行了以下研究以确定结合β-EP和N-Ac的功能意义。β-EP以剂量依赖性、纳洛酮不敏感的方式抑制植物血凝素（PHA）刺激的[3H]胸腺嘧啶核苷摄取。β-内啡肽1-27、（去）酪氨酸β-内啡肽2-31或N-Ac均未能复制β-EP的抑制作用。然而，在取代与鼠脾细胞或U937细胞结合的125I-β-EP方面与β-EP等效的N-Ac，拮抗了β-EP的抑制作用。结合先前的结合研究，目前的观察结果表明，β-EP对正常免疫细胞产生受体介导的反应，这些反应不依赖于对纳洛酮敏感的神经元样阿片受体的激活。与这种脑阿片受体结合极少的N-Ac是β-EP的纳洛酮不敏感免疫细胞受体的有效功能拮抗剂。
