BINDING OF [H-3] RO 16-6491, A REVERSIBLE INHIBITOR OF MONOAMINE-OXIDASE TYPE-B, TO HUMAN-BRAIN MITOCHONDRIA AND PLATELET MEMBRANES
BINDING OF [H-3] RO 16-6491, A REVERSIBLE INHIBITOR OF MONOAMINE-OXIDASE TYPE-B, TO HUMAN-BRAIN MITOCHONDRIA AND PLATELET MEMBRANES
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DOI：
10.1111/j.1471-4159.1987.tb13143.x
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发表时间：
1987-01-01
影响因子：
4.7
通讯作者：
DAPRADA, M
中科院分区：
文献类型：
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作者：
CESURA, AM;GALVA, MD;DAPRADA, M
B型单胺氧化酶（MAO-B）的可逆抑制剂[3 H]Ro 16-6491可特异性且高亲和力地结合人额叶皮质粗线粒体和血小板膜中的单一结合位点群体。在两种组织中，在20 ℃温育1小时后达到结合平衡。C.在20 ℃下，结合放射性的解离相对较快。而在0 ℃（t1/2 = 90-120分钟）时，C [3 H]Ro 16-6491具有缓慢解离配体的特征。MAO-B的抑制剂和底物抑制[3 H]Ro 16-6491的结合，而MAO-A阻断剂的效力低得多。Ro 16-6491也是MAO-B的底物，Ro 16-6491氧化的稳定的未鉴定中间体对酶具有高亲和力，这可能是该药物显著的MAO-B抑制作用的原因。根据这一假设，Ro 16-6491将表现为基于机制的可逆抑制剂。总之，[~ 3 H]Ro 16-6491选择性结合MAO-B，是研究正常和病理条件下该酶的区域组织分布的一种极好的新的放射性配体探针。
The reversible inhibitor of monoamine oxidase type B (MAO-B) [3H]Ro 16-6491 binds specifically and with high affinity to a single population of binding sites in human frontal cortex crude mitochondria and platelet membranes. In both tissues binding equilibrium was reached after 1 h incubation at 20.degree. C. Dissociation of bound radioactivity was relatively fast at 20.degree. C (t1/2 = 90-120 min) whereas at 0.degree. C [3H]Ro 16-6491 showed the characteristics of a slowly dissociating ligand. Inhibitors and substrates of MAO-B inhibited binding of [3H]Ro 16-6491, whereas MAO-A blockers were much less potent. Ro 16-6491 was also a substrate for MAO-B and a stable unidentified intermediate of the oxidation of Ro 16-6491 possessing high affinity for the enzyme may account for the marked MAO-B inhibitory effect of the drug. According to this hypothesis Ro 16-6491 would behave as a mechanism-based reversible inhibitor. In conclusion, [3H]Ro 16-6491 binds selectively to MAO-B and represents an excellent new radioligand probe for studing the regional tissue distribution of this enzyme in normal and pathological conditions.