Park C H, Lukacs L G, Mastropaolo J, Deutsch S I
Psychiatry Service, Department of Veterans Affairs Medical Center, Washington DC 20422, USA.
Isr J Psychiatry Relat Sci. 1997;34(4):300-7.
Monoamine Oxidase (MAO) and the peripheral benzodiazepine binding site (PBR) share a close physical proximity to each other in the outer mitochondrial membrane. Furthermore, MAO activity and the density of PBR sites are affected by stress; benzodiazepines may influence stress-induced changes in MAO activity. In view of the close physical association between MAO and the PBR, we examined the effects of chronic administration of selective and nonselective MAO inhibitors to mice on the specific binding of 3H-Ro5-4864 and 3H-PK-11195 to crude membranes prepared from kidney, heart and liver. Chronic MAO inhibition was associated with alterations in PBR binding in all three tissues; however, in heart and liver changes were not detectable with 3H-PK-11195. Perhaps, the ability to discern changes with 3H-Ro5-4864 that are not detectable with 3H-PK-11195 reflects a functional change in the "activity" of the PBR site in heart and liver that is elicited by chronic MAO inhibition and mediated by a change in the "conformation" of the protein that is detected with 3H-Ro5-4864. Importantly, iproniazid, the nonselective MAO inhibitor, caused changes in PBR binding in all three of the tissues.
单胺氧化酶（MAO）与外周苯二氮䓬结合位点（PBR）在外膜线粒体中彼此紧密相邻。此外，MAO活性和PBR位点密度受应激影响；苯二氮䓬可能影响应激诱导的MAO活性变化。鉴于MAO与PBR之间紧密的物理联系，我们研究了对小鼠长期给予选择性和非选择性MAO抑制剂，对从肾脏、心脏和肝脏制备的粗膜上3H-Ro5-4864和3H-PK-11195特异性结合的影响。长期MAO抑制与所有三个组织中PBR结合的改变有关；然而，在心脏和肝脏中，用3H-PK-11195未检测到变化。或许，用3H-Ro5-4864能够辨别而用3H-PK-11195无法检测到的变化，反映了心脏和肝脏中PBR位点“活性”的功能变化，这种变化由长期MAO抑制引发，并由用3H-Ro5-4864检测到的蛋白质“构象”变化介导。重要的是，非选择性MAO抑制剂异烟酰异丙肼在所有三个组织中均引起了PBR结合的变化。
