Selective effects of MAO inhibition on peripheral benzodiazepine receptor binding in the mouse.
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.
Park
C H
CH
Psychiatry Service, Department of Veterans Affairs Medical Center, Washington DC 20422, USA.
Lukacs
L G
LG
Mastropaolo
J
J
Deutsch
S I
SI
D000818:Animals; D001570:Benzodiazepinones / Q000493:pharmacokinetics*; D006321:Heart / Q000187:drug effects; D007546:Isoquinolines / Q000493:pharmacokinetics*; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects*
D001570:Benzodiazepinones; D007546:Isoquinolines; D008996:Monoamine Oxidase Inhibitors; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; C037850:PK 11195