Endogenous inhibitors of 4'-[³H]chlorodiazepam (Ro 5-4864) binding to 'peripheral' sites for benzodiazepines

'Peripheral' binding sites for benzodiazepines are under neural or homonal control in the pineal gland, olfactory bulb, and kidney. These observations prompted a search for an endogenous substance which could modulate these sites under physiological conditions. Acidified methanol extracts from several tissues (e.g. stomach, kidney, lung) were found to inhibit the binding of [³H]Ro 5-4864 to 'peripheral' binding sites, but did not significantly affect the binding of [³H]diazepam to 'brain' benzodiazepine receptors. Fractionation of a crude extract prepared from antral stomach by either ultrafiltration or gel filtration chromatography yielded high (M_r > 10000) and low (M_r < 1000) M_r fractions which competitively inhibited [³H]Ro 5-4864 binding to 'peripheral' sites. These observations suggest the presence of endogenous substances in several rat tissues which may represent physiologically important ligands for 'peripheral' binding sites for benzodiazepines.