(–)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={N. Bowery and D. Hill and A. Hudson and A. Doble and D. Middlemiss and J. Shaw and M. 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… Expand
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%. Expand
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. Expand
Pharmacology of GABAB Receptors
It is now about 20 years since we first examined the Cl−-dependent action of GABA on peripheral neurones and, in particular, on nerve terminals of sympathetic fibres. At the time we were trying toExpand
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. Expand
Cerebral GABAA and GABAB Receptors
y-Aminobutyric acid (GABA) is widely known as one of the major inhibitory neurotransmitters in the mammalian central nervous system (CNS).' In general, it has been considered that neuronal activityExpand
The Autoradiographic Localization of Baclofen-Sensitive GABAB Sites in Rat Cerebellum
The existence of a receptor for GABA on neurons of the mammalian peripheral and central nervous systems is now firmly established and radiolabelied ligand binding studies have supported the view thatExpand
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 (Bowery et al 1981; see Bowery 1989). In aExpand
A Brief History of the GABA B Receptor
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 receptorsExpand
Allosteric Modulation of GABAB Receptors
c-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system (CNS). A great number of major CNS-active, investigational, recreational, or clinicallyExpand
Bicuculline-insensitive GABA receptors on peripheral autonomic nerve terminals.
Data suggest the presence of a bicuculline-insensitive GABA receptor on autonomic nerve terminals, and preliminary observations indicate a lack of chloride ion dependence in the action of GABA at this site. Expand


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. Expand
Bicuculline, an antagonist of GABA and synaptic inhibition in the spinal cord of the cat.
The proposal is made that this amino acid, released at inhibitory axodendritic or axo-axonic synapses, is responsible for the prolonged inhibition of spinal motoneurones by repetitive impulses in afferent fibres (‘presynaptic’ inhibition). Expand
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 ofExpand
GABA Receptor in Rat Brain: Demonstration of an Antagonist Binding Site
A variety of evidence suggests that neurotransmitter receptors in the brain may exist in two interconvertible conformations, an agonist conformation with a selective high affinity for receptorExpand
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. Expand
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. Expand
Modulation of gamma-aminobutyric acid transport in nerve endings: role of extracellular gamma-aminobutyric acid and of cationic fluxes.
  • G. Levi, M. Raiteri
  • Medicine, Chemistry
  • 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. Expand
The action of β-phenyl-GABA derivatives on neurones of the cat cerebral cortex
The depressant action of β-p-CPG was not antagonised by bicuculline which suggests that the β-aryl-GABA derivatives do not exert a GABA-like action on cortical neurones. Expand
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). Expand
Action of baclofen on mammalian synaptic transmission
Microiontophoretic and systemic injections were used to investigate the mechanism of baclofen's powerful depressant action on transmission at primary afferent synapses in the cat and depressed the spontaneous and evoked activity of cuneate cells and reduced the excitability and input resistance of spinal motoneurones. Expand