Release of endogenous benzodiazepine receptor ligands (endozepines) from cultured neurons

Endozepines are naturally occurring small organic molecules, devoid of peptidic bonds and halogens, that act as allosteric modulators of the GABAA receptor through their actions at the benzodiazepine binding site. Endozepines are present in physiologically significant amounts in the brain and can act as potent positive allosteric modulators of the GABAA receptor. In this study, 3 endozepines present in cultured cerebellar granule cells were found to be released from neurons in a potassium-stimulated, calcium-dependent fashion. This release could also be mimicked by increasing concentrations of veratridine. Although endozepines were also found in cultured astrocytes, they could not be released in significant amounts by potassium depolarization. Differential release under depolarizing conditions and granule cell content of the various endozepines suggested a possible metabolic relationship between these two processes.