SELECTIVE EFFECTS OF MAO INHIBITION ON PERIPHERAL BENZODIAZEPINE RECEPTOR-BINDING IN THE MOUSE

Monoamine Oxidase (MAO) and the peripheral benzodiazepine binding site (PER) share a close physical proximity to each other in the outer mit ochondrial membrane. Furthermore, MAO activity and the density of PER sites are affected by stress; benzodiazepines may influence stress-ind uced changes in MAO activity. In view of the close physical associatio n between MAO and the PER, we examined the effects of chronic administ ration of selective and nonselective MAO inhibitors to mice on the spe cific binding of H-3-Ro5-4864 and H-3-PK-11195 to crude membranes prep ared from kidney, heart and liver. Chronic MAO inhibition was associat ed with alterations in PER binding in all three tissues; however, in h eart and liver changes were not detectable with H-3-PK-11195. Perhaps, the ability to discern changes with 3H-Ro5-4864 that are not detectab le with 3H-PK-11195 reflects a functional change in the ''activity'' o f the PER site in heart and liver that is elicited by chronic MAO inhi bition and mediated by a change in the ''conformation'' of the protein that is detected with H-3-Ro5-4864. importantly, iproniazid, the nons elective MAO inhibitor, caused changes in PER binding in all three of the tissues.