Oxytocin modulates glutamatergic synaptic transmission between cultured neonatal spinal cord dorsal horn neurons.
The functional characteristics of binding sites for the neuropeptide oxytocin (OT) detected by radioautography in laminae I and II of the dorsal horn (DH) and on cultured neonatal DH neurons were studied on the latter using perforated patch-clamp recordings. The neurons were identified by their spike discharge properties and on the basis of the presence of met-enkephalin-like and glutamate decarboxylase-like immunoreactivities. OT (100 nM) never induced any membrane current at a holding potential of -60 mV but increased the frequency of spontaneously occurring AMPA receptor-mediated EPSCs or the mean amplitude of electrically evoked EPSCs in a subset (35%) of neurons. The frequency of miniature EPSCs (m-EPSCs) recorded in the presence of 0.5 microM tetrodotoxin was also increased by OT (100 nM) without any change in their mean amplitude, indicating an action at a site close to the presynaptic terminal. The decay kinetics of any type of EPSC were never modified by OT. The effect of OT was reproduced by [Thr4, Gly7]-OT (100 nM), a selective OT receptor agonist, and blocked by d(CH2)5-[Tyr(Me)2,Thr4,Tyr-NH29]-ornithine vasotocin (100 nM), a specific OT receptor antagonist. Reducing the extracellular Ca2+ concentration from 2.5 to 0.3 mM in the presence of Cd2+ (100 microM) reversibly blocked the effect of OT on m-EPSCs. The OT receptors described here may represent the substrate for modulatory actions of descending hypothalamo-spinal OT-containing pathways on the nociceptive system.
Jo
Y H
YH
Laboratoire de Neurophysiologie Cellulaire et Intégrée, Unité Mixte de Recherche 7519-Centre National de la Recherche Scientifique, Université Louis Pasteur, 67084 Strasbourg Cedex, France.
Stoeckel
M E
ME
Freund-Mercier
M J
MJ
Schlichter
R
R
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001569:Benzodiazepines / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D004558:Electric Stimulation; D004744:Enkephalin, Methionine / Q000032:analysis / Q000276:immunology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000032:analysis / Q000276:immunology; D018698:Glutamic Acid / Q000502:physiology; D007150:Immunohistochemistry; D009474:Neurons / Q000737:chemistry* / Q000201:enzymology; D009619:Nociceptors / Q000502:physiology; D010121:Oxytocin / Q000031:analogs & derivatives* / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology*; D009435:Synaptic Transmission / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D001569:Benzodiazepines; C079692:GYKI 53655; D018698:Glutamic Acid; D013779:Tetrodotoxin; D010121:Oxytocin; D004744:Enkephalin, Methionine; C045427:oxytocin, Thr(4)-Gly(7)-; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D005968:Glutamate Decarboxylase; D002118:Calcium