Demonstration of Benzodiazepine-Like Molecules in the Mammalian Brain with a Monoclonal Antibody to Benzodiazepines

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 82; no. 16; pp. 5560 - 5564
• Main Authors: Sangameswaran, Lakshmi, De Blas, Angel L.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.08.1985; National Acad Sciences
• Subjects: Agonists; Animals; Antibodies; Antibodies, Monoclonal; Antigen-Antibody Complex; Benzodiazepines; Benzodiazepines - analysis; Binding sites; Biological and medical sciences; Brain; Brain - cytology; Brain - metabolism; Brain Chemistry; Cell physiology; Chromatography; Chromatography, Affinity; Epitopes; Fundamental and applied biological sciences. Psychology; Hybridomas - immunology; Ligands; Mice; Mice, Inbred BALB C; Molecular and cellular biology; Molecules; Neurotransmission; Receptors; Receptors, GABA-A - analysis; Immunocytochemistry; Rodentia; Central nervous system; Brain(Invertebrata); Identification; Monoclonal antibody; Vertebrata; Mammalia; Neuron; Mouse; Animal; Distribution; Benzodiazepine derivatives; Localization
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.82.16.5560

An anti-benzodiazepine monoclonal antibody has been used to demonstrate the existence of benzodiazepine-like molecules in the brain. Immunocytochemical experiments show that these molecules are neuronal and not glial and that they are ubiquitously distributed throughout the brain. Immunoblots indicate the presence of benzodiazepine-like epitopes in several brain peptides. Small benzodiazepine-like molecules were isolated from the brain soluble fraction by immunoaffinity chromatography. They block the binding of agonists, inverse agonists, and antagonists to the neuronal-type benzodiazepine receptor. The neurotransmitter γ -aminobutyric acid increases the affinity of the benzodiazepine receptor for the purified endogenous molecules. The results indicate that the immunoaffinity-purified molecules behave like the neuronal-type benzodiazepine receptor agonists. The purified molecules, however, do not inhibit the binding of tritiated Ro 5-4864 to the ``peripheral-type'' benzodiazepine receptor. The results demonstrate the existence of benzodiazepine-like molecules in the brain that bind to the benzodiazepine receptor. These molecules are different from the endogenous benzodiazepine receptor ligands reported by others.