Signal transduction by GABA(B) receptor heterodimers.

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Jones KA, Tamm JA, Craig DA, Ph D, Yao W, Panico R

Signal transduction by GABA(B) receptor heterodimers.

Neuropsychopharmacology. 2000 Oct;23(4 Suppl):S41-9.

PubMed ID

11008066 [ View in PubMed

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Abstract

GABA(B) receptors are G-protein-coupled receptors that mediate inhibition throughout the central and peripheral nervous systems. A single cloned receptor, GABA(B)R1, which has at least three alternatively spliced forms, appears to account for the vast majority of binding sites in the brain for high-affinity antagonists. In heterologous expression systems GABA(B)R1 is poorly expressed on the plasma membrane and largely fails to couple to ion channels. A second gene, GABA(B)R2, which exhibits moderately low homology to GABA(B)R1, permits surface expression of GABA(B)R1 and the appearance of baclofen-sensitive K(+) and Ca(+1) currents. We review the data that supports a model of the native GABA(B) receptor as a heterodimer composed of GABA(B)R1 and GABA(B)R2 proteins. New data from mutagenesis experiments are presented that point to amino acid residues on GABA(B)R1 critical for ligand activation of the heterodimer. The possible role of GABA(B)R2 in signal transduction is also discussed. The interdependent nature of the two subunits for receptor function makes the GABA(B) receptor a useful model to explore the larger significance of GPCR dimerization for G-protein activation.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Arbaclofen	Gamma-aminobutyric acid type B receptor subunit 2	Protein	Humans	Yes	Agonist	Details
Arbaclofen Placarbil	Gamma-aminobutyric acid type B receptor subunit 2	Protein	Humans	Yes	Agonist	Details