Effects of local administration of L-, N-, and P/Q-type calcium channel blockers on spontaneous dopamine release in the striatum and the substantia nigra: a microdialysis study in rat.
The pivotal role for voltage-sensitive calcium channels in initiating synaptic transmitter release is undisputed, but it is only partly known to what extent the different subtypes contribute in vivo. Their importance for the dendritic release of dopamine has not been investigated in vivo previously. To evaluate comprehensively the relative importance of different voltage-sensitive calcium channel subtypes for striatal dopamine release, and to further investigate the mechanism of dendritic dopamine release in the reticulate part of substantia nigra, dopamine was measured by in vivo microdialysis in the striatum or substantia nigra of awake rats. The calcium channel blockers nimodipine, omega-conotoxin-GVIA, omega-agatoxin-IVA, and neomycin were administered locally through the dialysis probes and compared with calcium-free perfusion. Results indicate that dopamine release in the striatum is mainly dependent on N- and P/Q-type channels, but the dendritic dopamine release in the substantia nigra is mediated mainly by some other calcium-dependent mechanism, for example, calcium mobilization through T-, O-, or R-type calcium channels. A portion of the dendritic release is calcium independent but can be inhibited partially by neomycin, which might suggest a role for inositol 4,5-bisphosphate breakdown products.
Bergquist
F
F
Institute of Physiology and Pharmacology, Department of Pharmacology, Göteborg University, Sweden.
Jonason
J
J
Pileblad
E
E
Nissbrandt
H
H
D000287:Administration, Topical; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004338:Drug Combinations; D008297:Male; D017551:Microdialysis; D009355:Neomycin / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013111:Spider Venoms / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA
D000900:Anti-Bacterial Agents; D002121:Calcium Channel Blockers; D004338:Drug Combinations; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D009553:Nimodipine; D020866:omega-Conotoxin GVIA; D009355:Neomycin; D004298:Dopamine