Type I and type II GABAA-benzodiazepine receptors produced in transfected cells.
GABAA (gamma-aminobutyric acid A)-benzodiazepine receptors expressed in mammalian cells and assembled from one of three different alpha subunit variants (alpha 1, alpha 2, or alpha 3) in combination with a beta 1 and a gamma 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 beta-carboline-3-carboxylate (beta-CCM) show a temperature-modulated selectivity for alpha 1 subunit-containing receptors. There were no significant differences in the binding of clonazepam, diazepam, Ro 15-1788, or dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) to all three recombinant receptors. Receptors containing the alpha 3 subunit show greater GABA potentiation of benzodiazepine binding than receptors containing the alpha 1 or alpha 2 subunit, indicating that there are subtypes within the type II class. Thus, diversity in benzodiazepine pharmacology is generated by heterogeneity of the alpha subunit of the GABAA receptor.
Pritchett
D B
DB
Department of Molecular Neuroendocrinology, Zentrum für Molekulare Biologie, Universität Heidelberg, Federal Republic of Germany.
Lüddens
H
H
Seeburg
P H
PH
D002460:Cell Line; D003975:Diazepam / Q000378:metabolism; D005442:Flumazenil / Q000378:metabolism; D005445:Flunitrazepam / Q000378:metabolism; D006801:Humans; D008970:Molecular Weight; D011724:Pyridazines / Q000378:metabolism; D011963:Receptors, GABA-A / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
D011724:Pyridazines; D011963:Receptors, GABA-A; D011994:Recombinant Proteins; D005442:Flumazenil; D005445:Flunitrazepam; C021604:CL 218872; D003975:Diazepam