Presynaptic 5-HT autoreceptors modulate N-methyl-D-aspartate-evoked 5-hydroxytryptamine release in the guinea-pig brain cortex.
Guinea-pig cerebral cortical slices preincubated with [3H]5-hydroxytryptamine ([3H]5-HT) were superfused with Mg(2+)-free Krebs' solution. N-Methyl-D-aspartate (NMDA) stimulated tritium overflow in a concentration-dependent manner. The NMDA-evoked overflow was abolished by omission of CA2+ or presence of 1.2 mM Mg2+, but only partly inhibited by tetrodotoxin. The competitive and noncompetitive NMDA receptor antagonists, DL-(E)-2-amino-4-methyl-5-phosphono-3-pentanoic acid (CGP 37849) and dizocilpine, respectively, also blocked the stimulatory effect of NMDA. Furthermore, the NMDA-evoked tritium overflow was inhibited by 5-carboxamidotryptamine in a manner susceptible to blockade by methiothepin, which given alone facilitated overflow. This facilitatory effect was increased in the presence of 6-nitroquipazine, a selective 5-HT reuptake inhibitor. It is concluded that the release of 5-HT in the guinea-pig cerebral cortex is stimulated via NMDA receptors, which are in part located on the serotoninergic axon terminals, and that the NMDA-evoked 5-HT release is modulated via inhibitory 5-HT autoreceptors.
Fink
K
K
Institut für Pharmakologie und Toxikologie, Universität Bonn, Germany.
Böing
C
C
Göthert
M
M
D000818:Animals; D017660:Autoreceptors / Q000502:physiology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism*; D004347:Drug Interactions; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014316:Tritium / Q000378:metabolism
D017660:Autoreceptors; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; D012701:Serotonin; D013779:Tetrodotoxin; D008719:Methiothepin; D016202:N-Methylaspartate