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A Brief History of the GABAB Receptor

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GABAB Receptor

Part of the book series: The Receptors ((REC,volume 29))

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Abstract

Discovery of the novel receptor for GABA, GABAB, arose during an attempt to model central primary afferent GABA receptors using sympathetic ganglia. The presence of chloride-dependent GABA receptors on ganglion cell bodies had been established in the early 1970s and this prompted us to consider the possibility that the receptors were also on the efferent nerve fibres of these cells and on the nerve terminal membranes. To pursue this, we examined the influence of GABA and its analogues on the evoked release of radiolabelled noradrenaline from sympathetic nerve fibres innervating rat isolated atria. A reduction in the release of noradrenaline would provide an indirect measure of receptor activation. As predicted, GABA reduced the evoked release but this effect was not blocked by GABA antagonists such as bicuculline and was not mimicked by muscimol but was mimicked by β-chlorophenyl GABA (baclofen). Further studies on the release of radiolabelled noradrenaline from rat brain cortex slices revealed a similar effect. Subsequently, in 1981, we were able to demonstrate the presence of a baclofen-sensitive 3H-GABA binding site on rat cortical membranes. It was at this stage we were able to designate this novel site ‘GABAB’ to contrast with the classical ‘GABAA’ site. The structure of this novel site only emerged some two decades later enabling a greater understanding of the potential physiological and pharmacological roles of the receptor to be made.

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  1. Medical School, University of Birmingham, Vincent Drive, Edgbaston, B15 2TT, UK

    Norman G. Bowery

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Correspondence to Norman G. Bowery .

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  1. Neuroscience Institute, National Research Council of Italy Neuroscience Institute, Cagliari, Italy

    Giancarlo Colombo

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Bowery, N.G. (2016). A Brief History of the GABAB Receptor. In: Colombo, G. (eds) GABAB Receptor. The Receptors, vol 29. Humana Press, Cham. https://doi.org/10.1007/978-3-319-46044-4_1

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