Premium
Effects of Ca 2+ antagonists on glutamate release and Ca 2+ influx in the hippocampus with in vivo intracerebral microdialysis
Author(s) -
Lu Y. Ming,
Zhang J. Tian,
Zhao F. Qing,
Qin Y. Fi
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12410.x
Subject(s) - microdialysis , veratridine , glutamate receptor , chemistry , extracellular , depolarization , nimodipine , calcium , channel blocker , voltage dependent calcium channel , neurotransmitter , nmda receptor , medicine , endocrinology , pharmacology , biophysics , biochemistry , biology , sodium , sodium channel , receptor , organic chemistry
1 The extracellular glutamate content and Ca 2+ level in vivo in rat hippocampus were measured by brain microdialysis following administration of two depolarizing agents (veratridine, KCl) and quinolinic acid (Quin). 2 The two depolarizing agents increased the extracellular glutamate level (to between 280 and 320% basal) and decreased the extracellular Ca 2+ content (to 48% of basal). However, Quin did not change the glutamate level but decreased the Ca 2+ content. 3 The effects of Ca 2+ antagonists on the changes of glutamate and Ca 2+ level were evaluated in this experimental model. At a dose of 0.5 mg kg −1 , i.v., nimodipine (L‐type channel blocker) did not produce significant changes in the stimulated‐glutamate release. A statistically significant inhibition of Ca 2+ influx was observed at a dose of 0.05 mg kg −1 . In contrast, in those animals receiving the N‐type Ca 2+ antagonist, daurisoline (0.1, 1 or 5 mg kg −1 , i.v.), a potent attenuation of both glutamate release and Ca 2+ influx was found. 4 We propose that the pharmacological properties of Ca 2+ influx and of neurotransmitter release differ and that nimodipine‐sensitive L‐type channels may not be very common in nerve terminals but are localized in cell soma. Daurisoline‐sensitive N‐type channels in nerve terminals have a much greater influence on excitatory amino acid release.