Benzodiazepine receptors: differential ligand interactions and purification of the receptor protein

The benzodiazepine receptor can be considered as a regulatory unit for GABA receptor function. Receptor agonists such as the classical benzodiazepines induce a conformational change of the receptor which results in an enhancement of GABAergic transmission, leading to therapeutically useful effects. Inverse agonists such as several beta-carboline derivatives induce a different conformational change of the receptor resulting in a reduction of GABAergic transmission with concomitant anxiogenic and convulsant effects. Antagonists like Ro 15-1788 largely lack drug efficacy per se but antagonize the action of agonists and inverse agonists by competitive interaction at the receptor. Highly purified benzodiazepine receptor fractions showed properties similar to those in intact neuronal membranes. The receptor fractions contained high affinity binding sites for benzodiazepine agonists, antagonists and inverse agonists which were amenable to modulation by GABA. In addition, high affinity sites for GABA were present. The progress made in the isolation of the GABA receptor complex raises hopes to determine the molecular details of receptor function and of drug efficacy in the near future.