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The FASEB Journal, Vol 1, 282-288, Copyright © 1987 by The Federation of American Societies for Experimental Biology
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SH Snyder, A Verma and RR Trifiletti
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
The peripheral-type benzodiazepine receptor is a site identified by its nanomolar affinity for [3H]diazepam, similar to the affinity of diazepam for the central-type benzodiazepine receptor in the brain. The peripheral-type benzodiazepine receptor occurs in many peripheral tissues but has discrete localizations as indicated by autoradiographic studies showing uniquely high densities of the receptors in the adrenal cortex and in Leydig cells of the testes. Subcellular localization studies reveal a selective association of the receptors with the outer membrane of mitochondria. Photoaffinity labeling of the mitochondrial receptor with [3H]flunitrazepam reveals two discrete labeled protein bands of 30 and 35 kDa, respectively. The 35-kDa band appears to be identical with the voltage-dependent anion channel protein porin. Fractionation of numerous peripheral tissues reveals a single principal endogenous ligand for the receptor, consisting of porphyrins, which display nanomolar affinity. Interactions of porphyrins with the mitochondrial receptor may clarify its physiological role and account for many pharmacological actions of benzodiazepines.
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