Skerritt J H, Macdonald R L
Eur J Pharmacol. 1984 May 18;101(1-2):135-41. doi: 10.1016/0014-2999(84)90039-6.
The effects of several beta-carboline and purine ligands for benzodiazepine receptors were studied upon GABA (4-aminobutyric acid) responses and upon diazepam enhancement of GABA responses, using mouse spinal cord neurons in dissociated cell culture. While the potent convulsant beta-carboline DMCM (methyl-6,7-dimethyoxy-4-ethyl-carboline-3-carboxylate), reduced GABA responses, methyl-carboline-3-carboxylate (beta CCMe) and the corresponding ethyl ester (beta CCEt) did not alter GABA responses. The propyl ester (beta CCPr) enhanced GABA responses in a concentration-dependent fashion, while both beta CCMe and beta CCPr blocked diazepam enhancement of GABA responses. beta CCPr may thus have partial agonist activity. Two purines with moderate benzodiazepine receptor affinity, 1-methylisoguanosine (MeIG) and 6-dimethylaminopurine (DMAP), weakly enhanced GABA responses. MeIG also significantly antagonized diazepam enhancement of GABA responses. Inosine and hypoxanthine had no apparent actions upon GABA responses or upon diazepam enhancement of such responses. The results with beta-carbolines are consistent with their behavioural profile in vivo and with neurochemical studies of their effects upon GABA-benzodiazepine receptor complexes. Furthermore, certain purines are also able to interact with these complexes.
利用解离细胞培养的小鼠脊髓神经元，研究了几种β-咔啉和嘌呤类苯二氮䓬受体配体对γ-氨基丁酸（GABA）反应以及地西泮增强GABA反应的影响。强效惊厥剂β-咔啉DMCM（甲基-6,7-二甲氧基-4-乙基-咔啉-3-羧酸酯）可降低GABA反应，而甲基-咔啉-3-羧酸酯（β-CCMe）和相应的乙酯（β-CCEt）则不改变GABA反应。丙酯（β-CCPr）以浓度依赖的方式增强GABA反应，而β-CCMe和β-CCPr均阻断地西泮对GABA反应的增强作用。因此，β-CCPr可能具有部分激动剂活性。两种对苯二氮䓬受体具有中等亲和力的嘌呤，1-甲基异鸟苷（MeIG）和6-二甲基氨基嘌呤（DMAP），微弱地增强了GABA反应。MeIG也显著拮抗地西泮对GABA反应的增强作用。肌苷和次黄嘌呤对GABA反应或地西泮对这种反应的增强作用没有明显影响。β-咔啉的结果与它们在体内的行为特征以及它们对GABA-苯二氮䓬受体复合物作用的神经化学研究一致。此外，某些嘌呤也能够与这些复合物相互作用。
