The function of metabotropic excitatory amino acid receptors in synaptic transmission in the thalamus: studies with novel phenylglycine antagonists.
The phenylglycines 3-hydroxyphenylglycine, 4-carboxy-3-hydroxy-phenylglycine (4C3HPG), 4-carboxyphenylglycine (4CPG) and alpha-methyl-4-carboxyphenylglycine (MCPG) were evaluated as putative selective antagonists of metabotropic glutamate receptors on single neurones of the ventrobasal thalamus of rats, with a view to using these compounds as tools to elucidate synaptic mechanisms in this brain area. The S-isomers of the latter three compounds were found to reduce excitations evoked by iontophoretically applied 1S,3R-ACPD, but not those evoked by ionotropic excitatory amino receptor agonists. When the antagonists were tested against sensory synaptic responses of ventrobasal neurones, it was found that responses evoked by noxious thermal stimulation of the peripheral receptive field were reduced in parallel with responses to 1S,3R-ACPD. In contrast, responses of neurones evoked by non-noxious (air-jet) stimuli were not reduced by the phenylglycine antagonists and 4C3HPG was found to enhance such responses, possibly by a presynaptic action mediated via mGluR2 receptors. The reductions of nociceptive responses are discussed in the context of antagonism of mGluR1 receptors, which are known to be numerous in the thalamus and located on post-synaptic dendrites. The involvement of such receptors in the nociceptive responses of thalamic neurones may be of considerable functional significance.
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Department of Visual Science, Institute of Ophthalmology, London, U.K.
Eaton
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D000200:Action Potentials / Q000187:drug effects; D000388:Air; D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006358:Hot Temperature; D007478:Iontophoresis; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*; D013788:Thalamus / Q000166:cytology / Q000502:physiology*
D001565:Benzoates; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C078245:4-carboxy-3-hydroxyphenylglycine; C079694:alpha-methyl-4-carboxyphenylglycine; C079693:4-carboxyphenylglycine; C023010:4-hydroxyphenylglycine; D005998:Glycine