A comparative phylogenetic study of the distribution of cerebellar GABAA/benzodiazepine receptors using radioligands and monoclonal antibodies

Abstract

In mammalian cerebella the distribution of high affinity GABAA and benzodiazepine binding sites does not parallel each other. Differences in the molecular structure of the receptor complex or conformational changes have been proposed to explain the lack of a co-localization of these binding sites. Using radio- and immunohistochemistry we were able to obtain similar results for cerebella of non-mammalian species, indicating that the respective distribution of the binding sites is well conserved throughout vertebrate evolution. The gamma-aminobutyric acid agonist [3H]muscimol and the beta-subunit specific antibody bd-17 strongly labeled the granular layer. The radioligands for the benzodiazepine binding site [3H]flunitrazepam and [3H]Ro 15-1788 revealed species variation in the ratio of benzodiazepine receptor density in the granular and molecular layers. In human and pig cerebellum, the localization of antigenic sites recognized by the alpha-subunit specific antibody bd-24 deviates from the distribution of the benzodiazepine binding sites.