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Endogenous inhibitors of 4'‐[ 3 H]chlorodiazepam (Ro 5‐4864) binding to ‘peripheral’ sites for benzodiazepines
Author(s) -
Mantione Charles R.,
Weissman Ben Avi,
Goldman Mark E.,
Paul Steven M.,
Skolnick Phil
Publication year - 1984
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(84)80913-8
Subject(s) - chemistry , endogeny , binding site , kidney , diazepam , ultrafiltration (renal) , receptor , capsaicin , sephadex , olfactory bulb , peripheral , benzodiazepine , pharmacology , biochemistry , medicine , endocrinology , central nervous system , biology , enzyme
‘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 [ 3 H]Ro 5‐4864 to ‘peripheral’ binding sites, but did not significantly affect the binding of [ 3 H]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 [ 3 H]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.