The ‘ABC’ of GABA receptors

doi:10.1016/S0165-6147(99)01413-3

Trends in Pharmacological Sciences

Volume 21, Issue 1, 1 January 2000, Pages 16-19

https://doi.org/10.1016/S0165-6147(99)01413-3 Get rights and content

Abstract

In the conventional view, GABA acts at either ionotropic GABA_A or metabotropic GABA_B receptors. Recently, novel ionotropic GABA receptors that are composed of ρ-subunits have been identified in the vertebrate retina. These bicuculline- and baclofen-insensitive GABA receptors are frequently called GABA_C, following an early suggestion by Graham Johnston and colleagues. An IUPHAR committee has recommended that the term GABA_C be avoided and subclassifies the retinal receptors as GABA_A0r. However, new evidence regarding the pharmacology, structure, function, genetics and cellular localization of ionotropic GABA receptors strengthens the case for the existence of two major classes of these receptors, GABA_A and GABA_C.

Section snippets

IUPHAR classification of GABA_A receptors

In a worthwhile attempt at the initial classification of a ligand-gated ion channel, a ‘provisional version’ of GABA_A receptor classification was published as an IUPHAR report¹⁵. On the basis of subunit structure and receptor function, this report, which was written by leading experts in the GABA_A field, has catagorized the αβγ-subunit-containing receptors as GABA_A1 to GABA_A6, according to the α-subunit present, and categorized the benzodiazepine-insensitive αβδ or αβϵ isoforms as GABA_A0

Pharmacology

GABA_C receptors are a pharmacologically distinct group. Whereas GABA_A and GABA_B receptors are defined by their respective sensitivities to bicuculline and baclofen3, 6, 7, 8, GABA_C receptors do not respond to either drug. The different pharmacological profiles of GABA_C and GABA_A receptors are illustrated in Table 1. Notably, CACA is a selective agonist for GABA_C receptors but inactive at GABA_A receptors, whereas the trans-enantiomer TACA shows no such preference6, 7, 9, 10. Furthermore, TPMPA

Concluding remarks

Are the ρ-subunit-containing GABA receptors best classified as a specialized set of GABA_A receptors, as provisionally proposed by the IUPHAR (Ref. 15)? Apparently not. Increasing knowledge of the differential pharmacology, structure, function, genetics and cellular localization of ionotropic GABA receptors already justifies the widely used GABA_C terminology. Revising the provisional recommendations of the IUPHAR committee on GABA receptor nomenclature will not only keep track with recent

Acknowledgements

The author thanks Arlene Hirano for helpful comments on the manuscript and acknowledges support from the Deutsche Forschungsgemeinschaft (SFB 509 ‘Neurovision’) and the Fonds der Chemischen Industrie.

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Trends in Pharmacological Sciences

ViewpointThe ‘ABC’ of GABA receptors

Abstract

Section snippets

IUPHAR classification of GABAA receptors

Pharmacology

Concluding remarks

Acknowledgements

Prog. Neurobiol.

Trends Neurosci.

Trends Pharmacol. Sci.

Trends Pharmacol. Sci.

Trends Pharmacol. Sci.

Trends Neurosci.

Prog. Retinal Eye Res.

Vis. Res.

Bioorg. Med. Chem. Lett.

Trends Neurosci.

Curr. Biol.

Genomics

GABAA receptor channels

Annu. Rev. Neurosci.

GABAC receptors: a novel receptor family with unusual pharmacology

News Physiol. Sci.

GABAC receptors: structure, function and pharmacology

Cloning of the γ-aminobutyric acid (GABA) ρ1 cDNA: a GABA receptor subunit highly expressed in the retina

Proc. Natl. Acad. Sci. U. S. A.

Viewpoint
The ‘ABC’ of GABA receptors

IUPHAR classification of GABA_A receptors

GABA_A receptor channels

GABA_C receptors: a novel receptor family with unusual pharmacology

GABA_C receptors: structure, function and pharmacology

Cloning of the γ-aminobutyric acid (GABA) ρ₁ cDNA: a GABA receptor subunit highly expressed in the retina