Porphyrins are endogenous ligands for the mitochondrial (peripheral-type) benzodiazepine receptor

'Peripheral-type' benzodiazepine receptors are localized to the outer mitochondrial membrane. We have identified potent competitive inhibitors of these receptors and purified them from human blood and from several rat organs. TLC analysis of the purified inhibitor from erythrocytes displays a single peak of inhibitory activity with an absorbance spectrum identical to hemin. All of the inhibitory activity in extracts of several tissues can be accounted for by their porphyrin and metalloporphyrin content. Pure hemin and protoporphyrin IX competitively inhibit mitochondrial benzodiazepine binding with K(i) values of 41 and 15 nM, respectively, and are less active by a factor of 1000 at central-type benzodiazepine receptors. Thus, porphyrins appear to be endogenous ligands for mitochondrial benzodiazepine receptors.