Pergamon Life Sciences, Vol. 54, No. 12, pp. 759-767, 1994 Copyright © 1994 Elsevier Science Ltd Printed in the USA. All rights reserved 0024-3205/94 $6.00 + .00 CHARACTERIZATION AND DIFFERENTIATION OF PERIPHERAL-TYPE BENZODIAZEPINE RECEPTORS IN RAT AND HUMAN PROSTATE A. Camins, F.X. Sureda, D. Pubill, J. Camarasa and ~E. Escubedo Laboratory of Pharmacology and Pharmacognosy. Faculty of Pharmacy. Univ. of Barcelona. Zona Univ. Pedralbes. 08028 Barcelona. Spain. (Received in final ~rm Janua~ 3, 1994) Summary We have characterized the presence of peripheral-type benzodiazepine receptor in rat and human prostate. [~H] PK 11195, a putative antagonist, showed a greater affinity for this receptor in rat prostate (KD = 1.71 ± 0.18 nM) than in human (KD = 15.23 ± 1.30 nM). In human, the peripheral-type benzodiazepine receptor density (Bm~ × = 13,575 f 1,929 fmols/mg) is double that in rat (B~a x = 6,345 ± 314 fmols/mg) . [3H] Ro 5-4864, an agonist, showed a low affinity (KD = 188.38 f 16.46 riM) for human peripheral-type benzodiazepine receptor subtype. We did not detect any difference between the population of this receptor in control human prostate and that in hyperplastic specimens. In rat, bound [~H] PK 11195 was partially inhibited by specific ligands of mitochondrial ADP/ATP carrier. This characteristic does not occur in human prostate. A common trait of both rat and human prostate peripheral-type benzodiazepine receptors is the competitive displacement of bound [~H] PK 11195 by nitrendipine and the blockers of the adenosine uptake system. Peripheral-type benzodiazepine receptors (PBR) have been described and/or characterized in several rat (1,2) and human tissues (3,4) . In 1986, Anholt (5) suggested an association of PBR with the outer mitochondrial membrane and Escubedo et al. (2) found modulation of [3H] Ro 5-4864 binding sites by atractyloside, a selective inhibitor of the ADP/ATP carrier, in rat vas deferens. Some pharmacological actions of drugs such as Ro 5-4864 and PK 11195 (specific ligands for this receptor subtype) have been described (6,7,8). In addition, a relationship between PBR and human steroidogenic organs has been postulated (9). Various studies have demonstrated marked species differences of PBR in certain brain areas and these differences can also be extended to the selective radioligands used in the binding assays (I) . Furthermore, increase on PBR density has been proposed as marker of brain damage. Peripheral-type benzodiazepines have high specific binding affinity for PBRs in glial tumors and Pappata et al. (I0) describe the utility of I'C-PK 11195 for imaging human glioma in conjunction with positron emission tomography. Katz et al. (ii) found an increase in PBR in human colonic adenocarcinoma, suggesting that these binding sites may be useful as tumor markers. The aim of the present study is to investigate and characterize the presence of PBR in rat and human prostate and to determine whether a human benign tumor process implies an increase in peripheral-type benzodiazepine binding site density. The different affinity between benzodiazepine and isoquinoline ligands in human tissue has been studied on the basis of [~H] RO 5-4864 and [3H] PK 11195 binding. Additionally, we have investigated the interaction of the rat and human PBR with some ligands of the mitochondrial ADP/ATP carrier, with protoporphyrin IX (the proposed endogenous ligand for this receptor subtype (12)) and with other compounds that, in previous studies, were found to affect peripheral-type benzodiazepine binding. IE. Escubedo. Lab. Pharmacology and Pharmacognosy. Faculty of Pharmacy. Univ. Barcelona. 08028 Barcelona. Spain.