Identification of inosine and hypoxanthine as endogenous ligands for the brain benzodiazepine-binding sites.

Abstract

Two endogenous ligands for the brain benzodiazepine-binding sites were isolated from bovine brain through gel filtration, paper electrophoresis, and paper chromatography. These ligands were identified as inosine and hypoxanthine, and both had a higher affinity for the brain benzodiazepine-binding sites than for benzodiazepine sites in some peripheral tissues. They did not bind to any other receptors tested, such as the opiate, muscarinic cholinergic, GABA and .beta.-adrenergic receptors. Both inosine and hypoxanthine competitively inhibited the binding of [3H]diazepam to the brain binding site. The benzodiazepine compounds, of which diazepam is a representative, have specific receptors in the CNS. These compounds exert anxiolytic, muscle relaxation, hypnotic and anticonvulsive effects.