Glutamate release in human cerebral cortex and its modulation by 5-hydroxtryptamine acting at h 5-HT(1D) receptors

Guido Maura, Manuela Marcoli, Massimo Tortarolo, Gian Carlo Andrioli, Maurizio Raiteri

Research output: Contribution to journalArticlepeer-review


1. The release of glutamic acid and its modulation by 5-hydroxytryptamine (5-HT) in the human brain has been investigated in synaptosomal preparations from fresh neocortical samples obtained from patients undergoing neurosurgery to reach deeply sited tumours. 2. The Ca2+-dependant K+ (15 mM)-evoked overflow of glutamate was inhibited by 5-HT in a concentration-dependant manner (EC50 = 2.9 nM; maximal effect ≃ 50%). The inhibition caused by 5-HT was antagonized by the 5-HT1/5-HT2 receptor antagonist methiothepin. The 5-HT(1B)/5-HT(1D) receptor agonist sumatriptan mimicked 5-HT (EC50 = 6.4 nM; maximal effect ≃ 50%); the effect of sumatriptan was also methiothepin-sensitive. Selective 5-HT(1A) receptor antagonists could not prevent the inhibition of glutamate release by 5-HT. 3. The 5-HT(1B)/5-HT(1D) receptor ligand GR 127935 and the 5-HT(2C)/5-HT(1B)/5-HT(1D) receptor ligand metergoline were able to prevent the 5-HT effect; instead they inhibited glutamate release, their effects being abolished by methiothepin. Some 5-HT(1A) receptor antagonists also displayed intrinsic agonist activity. 4. The effect of sumatriptan was prevented by ketanserin, a drug known to display much higher affinity for recombinant h 5-HT(1D) than for h 5-HT(1B) receptors. 5. We propose that neocortical glutamatergic nerve terminals in human brain cortex posses release-inhibiting presynaptic heteroreceptors that appear to belong to the h 5-HT(1D) subtype.

Original languageEnglish
Pages (from-to)45-50
Number of pages6
JournalBritish Journal of Pharmacology
Issue number1
Publication statusPublished - 1998


  • 5-hydroxytryptamine-glutamate interaction
  • Glutamate release
  • h 5-HT(1D) receptor
  • Human cerebral cortex
  • Human native 5-hydroxytryptamine receptors

ASJC Scopus subject areas

  • Pharmacology


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