(–)Baclofen decreases neurotransmitter release in the mammalian CNS by an action at a novel GABA receptor

@article{Bowery1980BaclofenDN,
  title={(–)Baclofen decreases neurotransmitter release in the mammalian CNS by an action at a novel GABA receptor},
  author={Norman G. Bowery and David R. Hill and Alan L. Hudson and A. T. A. Doble and Derek N. Middlemiss and John S. Shaw and M. J. Turnbull},
  journal={Nature},
  year={1980},
  volume={283},
  pages={92-94}
}
The existence of a receptor for γ-aminobutyric acid (GABA) on neurones of the mammalian central nervous system (CNS) is now firmly established1–3. It is generally accepted that bicuculline (and its methohalide salts) is an antagonist of the actions of GABA4,5, although resistance to bicuculline has been described6,7. The view that bicuculline prevents GABA from interacting with a membrane recognition site is supported by results obtained in radiolabelled ligand binding studies8,9. Bicuculline… 

Are baclofen-sensitive GABAB receptors present on primary afferent terminals of the spinal cord?

It is reported here that GABAB sites, unlike GABAA sites, are present in high concentrations in laminae I, II, III and IV of the dorsal horn and that after the neonatal administration of capsaicin this binding is reduced by 40–50%.

Pharmacology of GABAB Receptors

It is shown that GABA could indeed inhibit the evoked release of 3H-noradrenaline from sympathetic nerve terminals in isolated atria of the rat and that the clinically used GABA analogue, baclofen (β-chlorophenyl GABA), was stereospecifically active in suppressing the release of the sympathetic amine.

Direct hyperpolarizing action of baclofen on hippocampal pyramidal cells

The action of baclofen is analysed on the membrane potential of CA1 hippocampal pyramidal cells in vitro and it is reported that it directly hyperpolarizes these cells in a potent, stereoselective manner which is resistant to bicuculline methiodide.

3H-baclofen and 3H-GABA bind to bicuculline-insensitive GABAB sites in rat brain

It is reported that high-affinity saturable binding of 3H-baclof en and3H-G AB A to the GABAB site can be detected in fragments of crude synaptic membranes prepared from rat brain and that GABA and baclofen can compete for the same recognition site.

Cerebral GABAA and GABAB Receptors

Current concepts on GABA, and GAB& receptors in the mammalian CNS are described, with special reference to their pharmacological, neurochemical, and molecular biological characteristics.

The Autoradiographic Localization of Baclofen-Sensitive GABAB Sites in Rat Cerebellum

It was obviously of great interest to determine the morphological distribution of these receptor sites in the mammalian nervous system and this report summarizes some of the preliminary findings.

GABA B Receptor Control of Neurotransmitter Release in Mammalian Brain: Modification During Chronic Inflammation

The evidence for a GABA receptor which was distinct from the classical chloride-dependent ionotropic receptor first emerged in mammalian peripheral tissues and seemed unlikely that it had any physiological significance, perhaps with the exception of the enteric nervous system where GABA neurones have been demonstrated.

A Brief History of the GABA B Receptor

This work examined the influence of GABA and its analogues on the evoked release of radiolabelled noradrenaline from sympathetic nerve fibres innervating rat isolated atria and designated this novel receptor ‘GABAB’ to contrast with the classical ‘GABAA’ site.

Allosteric Modulation of GABAB Receptors

Barbiturates and benzodiazepines are in clinical use as anesthetic, anxiolytic, anticonvulsant, and muscle-relaxant agents, and both classes of drugs enhance the chloride conductance of the GABAA receptor, albeit through different mechanisms.

Bicuculline-insensitive GABA receptors on peripheral autonomic nerve terminals.

...

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    Proceedings of the National Academy of Sciences of the United States of America
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