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

  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},
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.




Use of 3H-muscimol for GABA receptor studies

Evidence of the binding of 3H-muscimol by brain tissue is presented, comparing binding by membrane preparations in vitro with retention of 3 H-musCimol after intravenous administration, and the ability of muscIMol to alter evoked release of GABA by synaptosomes is verified.

Evaluation of Bicuculline as a GABA Antagonist

THERE has been controversy recently about the reliability of bicuculline as an antagonist of the putative inhibitory transmitter γ-aminobutyric acid (GABA) in the brain1–3. Although the effects of

GABA Receptor in Rat Brain: Demonstration of an Antagonist Binding Site

An attempt was made to identify biochemically the antagonist binding site of the GABA receptor by using the GABA antagonist (+) bicuculline-methiodide as labelled ligand.

Gamma-aminobutyric acid binding to receptor sites in the rat central nervous system.

Gamma-aminobutyric acid binds to synaptic membrane fractions of rat brain in a selective fashion representing an interaction with postsynaptic GABA receptors, with intermediate values in the thalamus, hippocampus, hypothalamus, cerebral cortex, midbrain, and corpus striatum.

Presynaptic inhibition at the crayfish neuromuscular junction

Evidence for a presynaptic mechanism of a specific post-synaptic permeability increase (to K+ and/or Cl-) seems to be widespread in different species and has been demonstrated in the vertebrate heart, the mammalian central nervous system, in crustacea at neuromuscular junctions and nerve cell synapses, as well as in various other preparations.

Modulation of gamma-aminobutyric acid transport in nerve endings: role of extracellular gamma-aminobutyric acid and of cationic fluxes.

  • G. LeviM. Raiteri
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1978
It is concluded that the GABA transport system of nerve endings is susceptible to fine modulation by changes in cationic fluxes similar to those occurring in vivo during depolarization and repolarization.

Inhibition of Na+‐independent [3H]GABA binding to synaptic membranes of rat brain by β‐substituted GABA derivatives

The requirements of the substituents of the PC atom of the GABA molecule to retain affinity for the receptor sites are defined to achieve additional information on the mechanism of action of some GABA derivatives with central inhibitory activity, like P-phenyl-GABA (Phenygam) and fi-(p-chloropheny1)- GABA (Baclofen).