Effects of Ca2+ antagonists on glutamate release and Ca2+ influx in the hippocampus with in vivo intracerebral microdialysis.
1. The extracellular glutamate content and Ca2+ 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 Ca2+ content (to 48% of basal). However, Quin did not change the glutamate level but decreased the Ca2+ content. 3. The effects of Ca2+ antagonists on the changes of glutamate and Ca2+ 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 Ca2+ influx was observed at a dose of 0.05 mg kg-1. In contrast, in those animals receiving the N-type Ca2+ antagonist, daurisoline (0.1, 1 or 5 mg kg-1, i.v.), a potent attenuation of both glutamate release and Ca2+ influx was found. 4. We propose that the pharmacological properties of Ca2+ 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.
Lu
Y M
YM
Department of Molecular Pharmacology, Naval Neurobiology Research Centre, China Naval Medical College, Nanjing, China.
Zhang
J T
JT
Zhao
F Q
FQ
Qin
Y F
YF
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D044182:Benzylisoquinolines; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D003956:Dialysis; D005260:Female; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006624:Hippocampus / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D009553:Nimodipine / Q000494:pharmacology; D010477:Perfusion; D011189:Potassium Chloride / Q000494:pharmacology; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013238:Stereotaxic Techniques; D014701:Veratridine / Q000494:pharmacology
D000470:Alkaloids; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D005971:Glutamates; D009467:Neuromuscular Depolarizing Agents; D018377:Neurotransmitter Agents; D011805:Quinolinic Acids; D018698:Glutamic Acid; D009553:Nimodipine; D011189:Potassium Chloride; C023968:daurisoline; D014701:Veratridine; D017378:Quinolinic Acid; D002118:Calcium