L-type voltage-dependent calcium channels do not modulate aminergic neurotransmitter release induced by transient global cerebral ischaemia: an in vivo microdialysis study in rat.
Cerebral ischaemia induces considerable neurotransmitter exocytosis, mediated by calcium entry in neurones, essentially via the N-type, voltage-dependent channels, which are insensitive to calcium blockers. Nonetheless, these blockers, by unclear mechanisms, exert a neuroprotective effect when used in experimental ischaemic models. On the other hand, the existence of L-type, voltage-dependent channels, the only ones responding to the action of calcium blockers on synapses, argues in favour of their possible concomitant action in certain highly pathological situations. We studied the action of three calcium blockers, nimodipine, diltiazem and verapamil (administered at a concentration of 100 microM directly into the striatum of rats), on the extracellular release of dopamine and serotonin, and on the level of their main metabolites, in a model of transient global cerebral ischaemia (four-vessel occlusion). The total absence of effect of these molecules on neurotransmitter release induced by ischaemia proves the non-involvement of this mechanism in the protective action of calcium entry blockers on ischaemic lesions, and the absence or very weak action of L-type, voltage-dependent presynaptic channels in the striatum of rats.
Bentué-Ferrer
D
D
Laboratoire de Pharmacologie, UFR Médicale, Rennes, France.
Decombe
R
R
Saïag
B
B
Allain
H
H
Van den Driessche
J
J
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001682:Biological Availability; D015220:Calcium Channels / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003956:Dialysis; D004110:Diltiazem / Q000493:pharmacokinetics / Q000494:pharmacology; D007267:Injections; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009553:Nimodipine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014700:Verapamil / Q000493:pharmacokinetics / Q000494:pharmacology
D015306:Biogenic Monoamines; D015220:Calcium Channels; D018377:Neurotransmitter Agents; D009553:Nimodipine; D014700:Verapamil; D004110:Diltiazem