Multiple embryonic benzodiazepine binding sites: evidence for functionality.
We have found high-affinity binding (site-A) and low-affinity binding (site-B) of benzodiazepines to membrane homogenates of embryonic chick brain and spinal cord. A new technique was developed to permit the determination of complete electrophysiological dose-response curves on single neurons in cell culture, eliminating cell-to-cell variability as a problem that complicates the interpretation of pooled data. The electrophysiological potencies and binding affinities of a series of benzodiazepines correlate well for site-A but not for site-B or the micromolar site reported in adult rat brain. Site-A and the electrophysiological response are sensitive to photo-affinity blockade with flunitrazepam (FNZM) by about 75% while site-B is resistant to blockade. The FNZM-photolinked benzodiazepine receptor/GABA receptor complex is not chronically potentiated and thus exists in an 'unpotentiated' state. These experiments suggest that site-A in embryonic CNS membranes corresponds to a functional benzodiazepine receptor/GABA receptor complex in spinal cord cell cultures.
D000818:Animals; D001569:Benzodiazepines / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive; D001921:Brain / Q000196:embryology / Q000502:physiology*; D002642:Chick Embryo; D004594:Electrophysiology; D005445:Flunitrazepam / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010777:Photochemistry; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011963:Receptors, GABA-A; D013116:Spinal Cord / Q000187:drug effects / Q000196:embryology / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam