Petitto J M, Skolnick P, Arora P K
Laboratory of Neuroscience, National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, Maryland 20892.
Brain Behav Immun. 1989 Mar;3(1):39-46. doi: 10.1016/0889-1591(89)90004-4.
A dose-dependent (5-50 mg/kg) suppression of natural killer (NK) cell activity was observed 2 h after administration of the benzodiazepine receptor "inverse agonist" FG 7142 (N-methyl-beta-carboline-3-carboxamide), and was still manifest 24 h later. Addition of FG 7142 (1-1000 nM) to the 4 h 51 Cr release assay did not affect NK cell activity. Pretreatment of mice with the benzodiazepine receptor antagonist Ro 15-1788 (10 mg/kg) blocked FG 7142-induced suppression of NK cell activity, but had no effect when administered alone. The suppression of NK cell activity by FG 7142, a compound which produces a syndrome resembling stress or anxiety in both animals and man, provides further evidence that the central nervous system pathways subserved by the benzodiazepine/GABA receptor chloride channel complex ("supramolecular complex") may play a role in the modulation of immune function.
在给予苯二氮䓬受体“反向激动剂”FG 7142（N-甲基-β-咔啉-3-甲酰胺）2小时后，观察到自然杀伤（NK）细胞活性呈剂量依赖性（5 - 50毫克/千克）抑制，且24小时后仍很明显。在4小时的51铬释放试验中加入FG 7142（1 - 1000纳摩尔）并不影响NK细胞活性。用苯二氮䓬受体拮抗剂Ro 15 - 1788（10毫克/千克）预处理小鼠可阻断FG 7142诱导的NK细胞活性抑制，但单独给药时无作用。FG 7142是一种在动物和人类中都会产生类似应激或焦虑综合征的化合物，它对NK细胞活性的抑制进一步证明，由苯二氮䓬/GABA受体氯离子通道复合物（“超分子复合物”）所支持的中枢神经系统通路可能在免疫功能调节中发挥作用。
