Effects of Ca2+ channel antagonists on striatal dopamine and DOPA release, studied by in vivo microdialysis.
1. To elucidate the mechanisms regulating the release of striatal dopamine and its precursor, 3,4-dihydroxyphenylalanine (DOPA), we determined the effects of various Ca2+ channel antagonists, an N-type Ca2+ channel antagonist, omega-conotoxin GVIA, a P-type Ca2+ channel antagonist, omega-agatoxin IVA, and a Q-type Ca2+ channel antagonist, omega-conotoxin MVIIC, on the basal and Ca2+- and K+-evoked release of striatal dopamine and DOPA, by use of in vivo microdialysis. 2. Omega-conotoxin GVIA strongly inhibited striatal basal dopamine release (IC50 = 0.48 nM), whereas this toxin only weakly modulated basal striatal DOPA release (IC50 = 9.55 nM). Neither omega-agatoxin IVA nor omega-conotoxin MVIIC affected the basal striatal release of dopamine and DOPA. 3. Omega-conotoxin GVIA strongly inhibited Ca2+-evoked striatal dopamine release (IC50 = 0.40 nM), whereas Ca2+-evoked striatal DOPA release only was weakly modulated (IC50 = 10.51 nM). Neither omega-agatoxin IVA nor omega-conotoxin MVIIC affected the Ca2+-evoked release of striatal dopamine and DOPA. 4. Both omega-agatoxin IVA and omega-conotoxin MVIIC inhibited the K+-evoked release of striatal dopamine (IC50 of omega-agatoxin IVA = 2.65 nM; IC50 of omega-conotoxin MVIIC = 12.54 nM) and DOPA (IC50 of omega-agatoxin IVA = 0.15 nM; IC50 of omega-conotoxin MVIIC = 3.05 nM), whereas omega-conotoxin GVIA had no effect on the K+-evoked release of striatal dopamine and DOPA. 5. An increase in the extracellular Ca2+ and K+ concentrations (Ca2+- and K+-evoked stimulation) did not affect tyrosine hydroxylase activity in vivo. 6. These findings suggest that striatal DOPA release is neurotransmitter-like and that, unlike the mechanisms of striatal dopaminergic transmission, this striatal DOPA transmission is at least partly regulated by voltage-sensitive Ca2+ channels.
Okada
M
M
Department of Neuropsychiatry, School of Medicine, Hirosaki University, Japan.
Wada
K
K
Kiryu
K
K
Kawata
Y
Y
Mizuno
K
K
Kondo
T
T
Tasaki
H
H
Kaneko
S
S
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004058:Diffusion; D004295:Dihydroxyphenylalanine / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005071:Evoked Potentials / Q000187:drug effects; D005110:Extracellular Space; D008297:Male; D017551:Microdialysis; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002121:Calcium Channel Blockers; D004295:Dihydroxyphenylalanine; D014446:Tyrosine 3-Monooxygenase; D011188:Potassium; D002118:Calcium; D004298:Dopamine