Endogenous monoamines inhibit glutamate transmission in the spinal trigeminal nucleus of the guinea-pig.
1. With the use of whole-cell patch clamp recordings in slices of guinea-pig substantia gelatinosa (SG), we studied the serotonin (5-HT)- and noradrenaline (NA)-mediated inhibition of glutamate-mediated EPSCs evoked from primary afferent stimulation. 2. The frequency of spontaneous EPSPs was reduced by 5-HT and NA. 3. The inhibition of EPSCs caused by 5-HT was mediated by the 5-HT1D receptor subtype, since the 5-HT1D agonist, sumatriptan (1 microM), was effective. 4. NA and the alpha 2-agonist, 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK 14304), decreased the EPSCs and this inhibition was blocked by the alpha 2-antagonists, idazoxan (1 microM) and yohimbine (1 microM). 5. The 5-HT-releasing agent, fenfluramine (10 microM), and the Na-releasing agent, amphetamine (1 microM), also depressed EPSCs. Pretreatment of slices with the 5-HT-depleting agent, p-chloro-amphetamine (10 microM), attenuated the inhibition of fenfluramine but failed to antagonize the effects of exogenously applied 5-HT. 6. These in vitro results suggest that presynaptic inhibition of glutamate release from primary afferents can provide another mechanism to explain the antinociceptive effects of 5-HT and NA obtained in vivo.
Travagli
R A
RA
Vollum Institute, Oregon Health States University, Portland 97201, USA.
Williams
J T
JT
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D015306:Biogenic Monoamines / Q000502:physiology*; D004594:Electrophysiology; D005277:Fenfluramine / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology; D018408:Patch-Clamp Techniques; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology; D018490:Serotonin Agents / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013376:Substantia Gelatinosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014279:Trigeminal Nucleus, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D015306:Biogenic Monoamines; D017661:Receptors, Presynaptic; D018490:Serotonin Agents; D017366:Serotonin Receptor Agonists; D005277:Fenfluramine; D012701:Serotonin; D018698:Glutamic Acid; D009638:Norepinephrine