GABAA-receptors: drug binding profile and distribution of receptors containing the alpha 2-subunit in situ.
The highest structural diversity of GABAA-receptor subunits is observed among members of the alpha-subunit class. Using subunit-specific antisera, the receptors containing the alpha 2-subunit were characterized. Western blots revealed an apparent molecular size of 52 kDa for the alpha 2-subunit. Immunohistochemically, the alpha 2-subunit was most preponderant in areas which lack the alpha 1-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 alpha 2-subunit-specific antisera displayed a drug binding profile characterized by a low affinity for CL 218872, beta CCM and zolpidem. This is in striking contrast to the high affinities of these ligands displayed by receptors immunoprecipitated by the alpha 1-subunit-specific antiserum. Thus, the alpha 1- and the alpha 2-subunit characterize two GABAA-receptor populations which greatly differ in brain distribution and pharmacological profile.
Marksitzer
R
R
Institute of Pharmacology, University of Zürich, Switzerland.
Benke
D
D
Fritschy
J M
JM
Trzeciak
A
A
Bannwarth
W
W
Mohler
H
H
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D007106:Immune Sera / Q000276:immunology; D007124:Immunoenzyme Techniques; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011233:Precipitin Tests; D011869:Radioligand Assay; D051381:Rats; D011963:Receptors, GABA-A / Q000276:immunology / Q000378:metabolism*
D007106:Immune Sera; D010446:Peptide Fragments; D011963:Receptors, GABA-A