Presynaptic glutamate receptors facilitate release of norepinephrine and 5-hydroxytryptamine as well as dopamine in the normal and ischemic striatum

Kouichi Ohta, Yasuo Fukuuchi, Kunio Shimazu, Satoru Komatsumoto, Makoto Ichijo, Nobuo Araki, Mamoru Shibata

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


We investigated the effects of selective glutamate (Glu) agonists on the release of monoamine neurotransmitters and their implication in the enhanced monoamine release in cerebral ischemia. In the striatum of anesthetized Sprague-Dawley rats, in vivo microdialysis was performed and the release of excitatory amino acids (Glu and aspartate (Asp)) and monoamines (dopamine (DA), norepinephrine (NE) and 5-hydroxytryptamine (5-HT)) was measured by high-performance liquid chromatography with an electrochemical detector. (1) Forebrain ischemia by 4-vessel occlusion generated significant correlations between the Glu and Asp levels and the DA, NE and 5-HT levels (r = 0.922 ∼ 0.967, P < 0.01, n = 6). (2) l-Glu and its selective agonists (N-methyl-d-aspartate) (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and kainate (KA) evoked a simultaneous release of striatal DA, NE and 5-HT in a dose-dependent manner (P ' < 0.01, ANOVA, n - 8). The maximal monoamine release evoked by the Glu agonists showed different magnitudes in the order of DA >> NE > 5-HT (118-, 16- and 9-fold from the baseline levels by 62.5 mM l-Glu, respectively). Each Glu agonist exerted a different magnitude of transmitter release and the order of agonist efficacy was different among NE, 5-HT and DA release: AMPA = KA > l-Glu = NMDA for DA release, AMPA > l-Glu = NMDA = KA for NE release, and l-Glu = NMDA = KA = AMPA for 5-HT release. In conclusion, both presynaptic NMDA and AMPA/KA receptors regulating the transmitter release exist widely on the monoaminergic (DA, NE and 5-HT) nerve terminals in the rat striatum, with a variety of receptor subtypes and variation in the agonist efficacy. Their implication in the augmentation of monoamine release in cerebral ischemia was suggested.

Original languageEnglish
Pages (from-to)195-202
Number of pages8
JournalJournal of the Autonomic Nervous System
Issue numberSUPPL.
Publication statusPublished - 1994 Sept


  • Excitatory amino acid
  • Kainate
  • Monoamine
  • N-Methyl-d-aspartate
  • Nerve terminal
  • α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

ASJC Scopus subject areas

  • General Neuroscience
  • Physiology
  • Clinical Neurology


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