Glutamate release in human cerebral cortex and its modulation by 5-hydroxtryptamine acting at h 5-HT1D receptors

被引:59
作者
Maura, G
Marcoli, M
Tortarolo, M
Andrioli, GC
Raiteri, M
机构
[1] Univ Genoa, Inst Pharmacol & Toxicol, I-16148 Genoa, Italy
[2] Galliera Hosp, Div Neurosurg, I-16128 Genoa, Italy
关键词
human cerebral cortex; glutamate release; 5-hydroxytryptamine-glutamate interaction; human native 5-hydroxytryptamine receptors; h 5-HT1D receptor;
D O I
10.1038/sj.bjp.0701581
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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+-dependent K+ (15 mM)-evoked overflow of glutamate was inhibited by 5-HT in a concentration-dependent manner (EC50 = 2.9 nM; maximal effect similar or equal to 50%). The inhibition caused by 5-HT was antagonized by the 5-HT1/5-HT2 receptor antagonist methiothepin. The 5-HT1B/5-HT1D receptor agonist sumatriptan mimicked 5-HT (EC50= 6.4 nM; maximal effect similar or equal to 50%); the effect of sumatriptan was also methiothepin-sensitive. Selective 5-HT1A receptor antagonists could not prevent the inhibition of glutamate release by 5-HT. 3 The 5-HT1B/5-HT1D receptor ligand GR 127935 and the 5-HT2C/5-HT1B/5-HT1D receptor ligand metergoline were unable to prevent the 5-HT effect; instead they inhibited glutamate release, their effects being abolished by methiothepin. Some 5-HT1A 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-HT1D than for h 5-HT1B receptors. 5 We propose that neocortical glutamatergic nerve terminals in human brain cortex possess release-inhibiting presynaptic heteroreceptors that appear to belong to the h 5-HT1D subtype.
引用
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页码:45 / 50
页数:6
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