Cloning of cDNA sequences encoding human alpha 2 and alpha 3 gamma-aminobutyric acidA receptor subunits and characterization of the benzodiazepine pharmacology of recombinant alpha 1-, alpha 2-, alpha 3-, and alpha 5-containing human gamma-aminobutyric acidA receptors.

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Hadingham KL, Wingrove P, Le Bourdelles B, Palmer KJ, Ragan CI, Whiting PJ

Mol Pharmacol. 1993 Jun;43(6):970-5.

PubMed ID

8391122 [ View in PubMed

]

Abstract

cDNAs encoding human alpha 2 and alpha 3 gamma-aminobutyric acidA receptor subunits have been cloned. Their deduced amino acid sequences show much sequence identity with the published bovine sequences (98.2% and 97.0% for alpha 2 and alpha 3, respectively). Human alpha 1 beta 1 gamma 2, alpha 2 beta 1 gamma 2, alpha 3 beta 1 gamma 2, and alpha 5 beta 1 gamma 2 subunit combinations were expressed in transiently transfected cells and their pharmacologies were characterized using a series of benzodiazepine (BZ) binding site ligands. Human alpha 1-containing receptors exhibited a BZ1-type pharmacology, and alpha 2-, alpha 3-, and alpha 5-containing receptors exhibited a broadly BZ2-type pharmacology. The partial inverse agonist Ro15-4513 showed an approximately 10-15-fold higher affinity for alpha 5-containing than for alpha 1-, alpha 2-, or alpha 3-containing receptors and is thus the first compound shown to have a significantly higher affinity for another receptor subtype than for alpha 1 beta 1 gamma 2.

DrugBank Data that Cites this Article

Polypeptides

Name	UniProt ID
Gamma-aminobutyric acid receptor subunit alpha-2	P47869	Details
Gamma-aminobutyric acid receptor subunit alpha-3	P34903	Details

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Zolpidem	Gamma-aminobutyric acid receptor subunit alpha-1	Ki (nM)	111.9	N/A	N/A	Details
Zolpidem	Gamma-aminobutyric acid receptor subunit alpha-3	Ki (nM)	2149.5	N/A	N/A	Details