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Type I and Type II GABA A -Benzodiazepine Receptors Produced in Transfected Cells

1989; American Association for the Advancement of Science; Volume: 245; Issue: 4924 Linguagem: Inglês

10.1126/science.2551039

1095-9203

Dolan B. Pritchett, Hartmut Lüddens, Peter H. Seeburg,

Neurotransmitter Receptor Influence on Behavior

GABA A (γ-aminobutyric acid A)-benzodiazepine receptors expressed in mammalian cells and assembled from one of three different α subunit variants (α 1 , α 2 , or α 3 ) in combination with a β 1 and a γ 2 subunit display the pharmacological properties of either type I or type II receptor subtypes. These receptors contain high-affinity binding sites for benzodiazepines. However, CL 218 872, 2-oxoquazepam, and methyl β-carboline-3-carboxylate (β-CCM) show a temperature-modulated selectivity for α 1 subunit-containing receptors. There were no significant differences in the binding of clonazepam, diazepam, Ro 15-1788, or dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM) to all three recombinant receptors. Receptors containing the α 3 subunit show greater GABA potentiation of benzodiazepine binding than receptors containing the α 1 or α 2 subunit, indicating that there are subtypes within the type II class. Thus, diversity in benzodiazepine pharmacology is generated by heterogeneity of the α subunit of the GABA A receptor.