Distribution, prevalence, and drug binding profile of gamma-aminobutyric acid type A receptor subtypes differing in the beta-subunit variant.
Native gamma-aminobutyric acid type A (GABAA) receptors containing different beta-subunit variants were identified immunobiochemically with antisera recognizing selectively the beta 1-, beta 2-, or beta 3-subunit. As determined by immunoprecipitation, the beta 2-subunit was present in 55-60% of GABAA receptors, while only minor receptor populations contained the beta 1-subunit (16-18%) or the beta 3-subunit (19-25%). Since the sum of these values amounts to about 100%, it is concluded that GABAA receptors largely contain only a single type of beta-subunit. Pharmacologically, receptors containing the beta 2-subunit differed from those containing the beta 1- or beta 3-subunit by their differential affinities for benzodiazepine receptor ligands. The subunit composition was analyzed biochemically in receptors immunoprecipitated by the beta 2-subunit antiserum. The beta 2-subunit was preferentially associated with the alpha 1-subunit (rarely with the alpha 2-subunit) and with the gamma 2-subunit; negligible or no immunoreactivity was detected for the alpha 3-, alpha 5-, or beta 1-subunit. A stringent co-expression of alpha 1- and beta 2-subunits was confirmed by double immunofluorescence staining on the cellular level. Neurons expressing the beta 3-subunit immunoreactivity were largely double labeled by the alpha 2-subunit antiserum. Thus, the subunit combinations alpha 1 beta 2 gamma 2 and alpha 2 beta 3 gamma 2 represent two main GABAA receptor subtypes, which together amount to 75-85% of the diazepam-sensitive GABAA receptors.
Benke
D
D
Institute of Pharmacology, ETH and University of Zurich, Switzerland.
Fritschy
J M
JM
Trzeciak
A
A
Bannwarth
W
W
Mohler
H
H
D000818:Animals; D001923:Brain Chemistry; D002243:Carbolines / Q000378:metabolism; D005442:Flumazenil / Q000378:metabolism; D005445:Flunitrazepam / Q000378:metabolism; D014644:Genetic Variation; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D008970:Molecular Weight; D011233:Precipitin Tests; D011487:Protein Conformation; D011724:Pyridazines / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000145:classification / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D014018:Tissue Distribution; D000077334:Zolpidem
D002243:Carbolines; D011724:Pyridazines; D011725:Pyridines; D011963:Receptors, GABA-A; D005442:Flumazenil; D005445:Flunitrazepam; C021604:CL 218872; D000077334:Zolpidem; C036150:beta-carboline-3-carboxylic acid methyl ester