Interactions between metabotropic and ionotropic glutamate receptor agonists in the rat spinal cord in vivo.
Microelectrophoretic application of the non-selective metabotropic glutamate receptor (mGluR) agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD] and the group I selective mGluR agonist (RS)-3,5-dihydroxyphenylglycine [(RS)-3,5-DHPG] potentiated the responses of rat spinal neurones to the cyclically-ejected ionotropic excitatory amino acid (EAA) agonists NMDA, AMPA and kainate in vivo. Potentiation was not selective between the three ionotropic responses and was paralleled by an enhancement of background activity in spontaneously active cells. "Correcting" spike count data for this increase in background activity showed that the EAA responses were not potentiated beyond the apparent enhancement of cell excitability. Neither mGluR agonist produced potentiation when NMDA/AMPA cycling was superimposed on background discharge held constant with kainate. It is concluded that potentiation produced by both (1S,3R)-ACPD and (RS)-3,5-DHPG is secondary to an enhancement of cell excitability rather than being due to a specific interaction with ionotropic EAA receptors. The mechanism of excitability enhancement cannot be determined by extracellular recording, but group I mGluRs are most likely to be responsible.
Department of Physiology, School of Medical Sciences, University of Bristol, UK.
M W
MW
Jones
P M
PM
Headley
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004586:Electrophoresis; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D012118:Resorcinols / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C079215:3,5-dihydroxyphenylglycine; D005998:Glycine