![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
H Luddens, PH Seeburg and ER Korpi
Laboratory of Molecular Neuroendocrinology, Center for Molecular Biology, Heidelberg, Germany.
We expressed in cultured cells recombinant gamma-aminobutyric acid type A (GABAA) receptors of the subunit compositions alpha 1 beta j gamma k and alpha 5 beta j gamma k (j = 1, 2, or 3 and k = 2 or 3). A comparison of ligand-binding properties revealed a functional role for individual beta variants, which depended on the alpha subunit in the GABAA receptor. Recombinant alpha 5 beta x gamma 2/3 receptors recognized the cage convulsant t-butylbicyclophosphoro[35S]thionate, as well as the benzodiazepine (BZ) receptor inverse agonist [3H]Ro 15- 4513, only with the beta 3 variant. In contrast, the exchange of beta variants in alpha 1 beta x gamma 2 receptors imparted differential modulation of t-butyl-bicyclophosphoro[35S]thionate binding by BZ receptor ligands. The BZ site of gamma 3-containing receptors was partially independent of the accompanying alpha and beta variants. alpha 1/5 beta 3 gamma 3 receptors were zolpidem insensitive but distinguished from alpha 5 beta 3 gamma 2 receptors by high affinity for the partial BZ receptor agonist CI 218,872. The distinct affinities of recombinant receptors for CI 218,872 suggested that the alpha 5 beta 3 gamma 2 receptor is the dominant zolpidem-insensitive GABAA receptor in the brain. Hence, alpha 5 beta 3 gamma 3 recpetors are not a major fraction of the native zolpidem-insensitive receptors, even though their genes are colocalized on mouse chromosome 7 and on human chromosome 15.
This article has been cited by other articles:
|
|
 |
|
  F. Sancar, S. S. Ericksen, A. M. Kucken, J. A. Teissere, and C. Czajkowski Structural Determinants for High-Affinity Zolpidem Binding to GABA-A receptors Mol. Pharmacol., January 1, 2007; 71(1): 38 - 46. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. B. Caraiscos, E. M. Elliott, K. E. You-Ten, V. Y. Cheng, D. Belelli, J. G. Newell, M. F. Jackson, J. J. Lambert, T. W. Rosahl, K. A. Wafford, et al. Tonic inhibition in mouse hippocampal CA1 pyramidal neurons is mediated by {alpha}5 subunit-containing {gamma}-aminobutyric acid type A receptors PNAS, March 9, 2004; 101(10): 3662 - 3667. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. I. Strakhova, S. C. Harvey, C. M. Cook, J. M. Cook, and P. Skolnick A Single Amino Acid Residue on the alpha 5 Subunit (Ile215) Is Essential for Ligand Selectivity at alpha 5beta 3gamma 2gamma -Aminobutyric AcidA Receptors Mol. Pharmacol., April 13, 2001; 58(6): 1434 - 1440. [Abstract] [Full Text]
|
|
|
|
|
|
M. Davies, J. G. Newell, J. M. C. Derry, I. L. Martin, and S. M. J. Dunn Characterization of the Interaction of Zopiclone with gamma -Aminobutyric Acid Type A Receptors Mol. Pharmacol., October 1, 2000; 58(4): 756 - 762. [Abstract] [Full Text]
|
|
|
|
|
|
K. Baer, C. Essrich, J. A. Benson, D. Benke, H. Bluethmann, J.-M. Fritschy, and B. Luscher Postsynaptic clustering of gamma -aminobutyric acid type A receptors by the gamma 3 subunit in vivo PNAS, October 26, 1999; 96(22): 12860 - 12865. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. I. Tietz, J. Kapur, and R. L. Macdonald Functional GABAA Receptor Heterogeneity of Acutely Dissociated Hippocampal CA1 Pyramidal Cells J Neurophysiol, April 1, 1999; 81(4): 1575 - 1586. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Sur, K. Quirk, D. Dewar, J. Atack, and R. McKernan Rat and Human Hippocampal alpha 5 Subunit-Containing gamma -Aminobutyric AcidA Receptors Have alpha 5beta 3gamma 2 Pharmacological Characteristics Mol. Pharmacol., November 1, 1998; 54(5): 928 - 933. [Abstract] [Full Text]
|
|
|
|
 |
|
 T. R. Neelands, L. J. Greenfield Jr, J. Zhang, R. S. Turner, and R. L. Macdonald GABAA Receptor Pharmacology and Subtype mRNA Expression in Human Neuronal NT2-N Cells J. Neurosci., July 1, 1998; 18(13): 4993 - 5007. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Barnard, P. Skolnick, R. W. Olsen, H. Mohler, W. Sieghart, G. Biggio, C. Braestrup, A. N. Bateson, and S. Z. Langer International Union of Pharmacology. XV. Subtypes of gamma -Aminobutyric AcidA Receptors: Classification on the Basis of Subunit Structure and Receptor Function Pharmacol. Rev., June 1, 1998; 50(2): 291 - 314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Ebert, S. A. Thompson, K. Saounatsou, R. McKernan, P. Krogsgaard-Larsen, and K. A. Wafford Differences in Agonist/Antagonist Binding Affinity and Receptor Transduction Using Recombinant Human gamma -Aminobutyric Acid Type A Receptors Mol. Pharmacol., December 1, 1997; 52(6): 1150 - 1156. [Abstract] [Full Text]
|
|
|
|
 |
|
 P. Skolnick, R. J. Hu, C. M. Cook, S. D. Hurt, J. D. Trometer, R. Liu, Q. Huang, and J. M. Cook [3H]RY 80: A High-Affinity, Selective Ligand for gamma -Aminobutyric AcidA Receptors Containing Alpha-5 Subunits, J. Pharmacol. Exp. Ther., November 1, 1997; 283(2): 488 - 493. [Abstract] [Full Text]
|
|
|
|
|
|
P. B. Wingrove, S. A. Thompson, K. A. Wafford, and P. J. Whiting Key Amino Acids in the gamma Subunit of the gamma -Aminobutyric AcidA Receptor that Determine Ligand Binding and Modulation at the Benzodiazepine Site Mol. Pharmacol., November 1, 1997; 52(5): 874 - 881. [Abstract] [Full Text]
|
|
|
|
|
|
A. Buhr and E. Sigel A point mutation in the gamma 2 subunit of gamma -aminobutyric acid type A receptors results in altered benzodiazepine binding site specificity PNAS, August 5, 1997; 94(16): 8824 - 8829. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Buhr, R. Baur, and E. Sigel Subtle Changes in Residue 77 of the gamma Subunit of alpha 1beta 2gamma 2 GABAA Receptors Drastically Alter the Affinity for Ligands of the Benzodiazepine Binding Site J. Biol. Chem., May 2, 1997; 272(18): 11799 - 11804. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. E. Homanics, T. M. DeLorey, L. L. Firestone, J. J. Quinlan, A. Handforth, N. L. Harrison, M. D. Krasowski, C. E. M. Rick, E. R. Korpi, R. Makela, et al. Mice devoid of gamma -aminobutyrate type A receptor beta 3 subunit have epilepsy, cleft palate, and hypersensitive behavior PNAS, April 15, 1997; 94(8): 4143 - 4148. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
