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Current Topics in Pharmacology   Volumes    Volume 4 
Heterogeneity of the GABAA receptors: pharmacological and molecular views
Diego Ruano, Francisco Araujo Rachid Bentareha, Javier Vitorica
Pages: 87 - 96
Number of pages: 10
Current Topics in Pharmacology
Volume 4 

Copyright © 1998 Research Trends. All rights reserved

The molecular composition of the γ-aminobutyric acid type A (GABAA) receptors, strongly determines both the electrophysiological and pharmacological properties of these receptors. Pharmacologically three types of GABAA receptors have been identified according to their affinities for the imidazopiridazine zolpidem; type I, with high affinity, type IIM, with medium affinity and type IIL with low affinity for this compound. However, a total of fifteen subunits belonging to GABAA receptors (α1-6, β1-3, γ1-3, δ and ε) have been cloned. A minimum of αβγ subunit combination is needed to resembled all the properties of the native GABAA receptors, suggesting that a high theoretical number of GABAA receptors could exist. Thus, the predicted number of GABAA receptors from molecular data is higher than the pharmacological classification. The absence of specific tools, as isotype selective compounds, has strongly limited the advance in the discovery of new pharmacologically different GABAA receptors. Furthermore, in the last years molecular data have revealed the existence of native GABAA receptors made up by two different alpha subunits in the same receptor complex, introducing a new level of complexity in the molecular composition of the GABAA receptors. In this case, both the pharmacological and physiological properties need to be determined.
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