GABAA-Receptors: Drug Binding Profile and Distribution of Receptors Containing the α2-Subunit in Situ

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Abstract
The highest structural diversity of GABAA-receptor subunits is observed among members of the α-subunit class. Using subunit-specific antisera, the receptors containing the α2-subunit were characterized. Western blots revealed an apparent molecular size of 52 kDa for the α2-subunit. Immunohistochemically, the α2-subunit was most preponderant in areas which lack the α1-subunit, e.g. striatum and olfactory bulb granule cell layer, suggesting that these two subunits represent largely distinct receptor subtypes. Pharmacologically, the receptor population which was immunoprecipitated by the α2-subunit-specific antisera displayed a drug binding profile characterized by a low affinity for CL 218872, βCCM and zolpidem. This is in striking contrast to the high affinities of these ligands displayed by receptors immunoprecipitated by the α1-subunit-specific antiserum. Thus, the α-and the α2-subunit characterize two GABAA-receptor populations which greatly differ in brain distribution and pharmacological profile.