Serotonin suppresses N-methyl-D-aspartate responses in acutely isolated spinal dorsal horn neurons of the rat.
In acutely isolated spinal dorsal horn neurons of the rat, effects of serotonin (5-hydroxytryptamine, 5-HT) on inward current induced by excitatory amino acids were studied under whole-cell voltage-clamp condition. 5-HT suppressed the response to N-methyl-D-aspartate (NMDA), but not the response to kainate or quisqualate. This inhibitory effect of 5-HT on NMDA response was present at 5-HT concentrations as low as 10(-15) M. Although the 5-HT effect exhibited similar pharmacology to the 5-HT1A-type receptors, it was not mimicked by increasing intracellular concentration of adenosine 3',5'-cyclic monophosphate that is the common second messenger for 5-HT1A receptors in the mammalian central nervous system. Glycine strongly antagonized this inhibitory effect of 5-HT, and 5-HT reduced opening of NMDA-gated single channels recorded from the outside-out membrane patch. These lines of evidence are consistent with a possibility that 5-HT might directly modulate the NMDA receptor-ion channel complex, either by interacting with the regulatory site(s) or by acting on a distinct site.
Murase
K
K
Department of Information Science, Fukui University, Japan.
Randic
M
M
Shirasaki
T
T
Nakagawa
T
T
Akaike
N
N
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D004357:Drug Synergism; D005998:Glycine / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D009474:Neurons / Q000187:drug effects*; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D000077526:Tropisetron
D007211:Indoles; D016194:Receptors, N-Methyl-D-Aspartate; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D015124:8-Bromo Cyclic Adenosine Monophosphate; D012701:Serotonin; D016202:N-Methylaspartate; D000077526:Tropisetron; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D016318:Quisqualic Acid; D007650:Ketanserin; D007608:Kainic Acid; D005998:Glycine