Presynaptic L-type Ca(2)+ channels on excessive dopamine release from rat caudate putamen.
We investigated by means of behavioral and neurochemical studies the role of the nerve terminal L-type voltage sensitive Ca(2)+ channel on dopamine (DA) release. Microinjection of Bay K 8644 (BAYK), an L-type Ca(2)+ channel stimulant, into the rat caudate putamen increased locomotor activity and rearing behavior in a dose-dependent manner, whereas injections into the amygdala had no effect. DA receptor antagonists significantly blocked BAYK-induced hyperactivity. Significant increases of extracellular DA levels were detected by microdialysis 20 min after BAYK administration into caudate putamen and then declined. This increase was influenced by tetrodotoxin, an axonal Na(+) channel blocker. Pretreatment with nimodipine and nicardipine, but not nifedipine, which are 1, 4-dihydropyridine L-type Ca(2)+ channel antagonists, administered into the caudate putamen significantly blocked BAYK-induced hyperactivity and DA efflux. These results indicate that the extraordinary DA release in the caudate putamen was mediated by extreme stimulation of the nicardipine and nimodipine-sensitive L-type Ca(2)+ channel present in the nerve terminal of striatal DA neurons.
Okita
M
M
Department of Internal Medicine III, Tokyo Medical University, 6-7-1, Nishi-Shinjuku, Shinjuku-ku, Tokyo, Japan.
Watanabe
Y
Y
Taya
K
K
Utsumi
H
H
Hayashi
T
T
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000008:administration & dosage; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000008:administration & dosage; D002121:Calcium Channel Blockers / Q000008:administration & dosage; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000008:administration & dosage; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism; D008024:Ligands; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D017729:Presynaptic Terminals / Q000378:metabolism*; D011699:Putamen / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin / Q000008:administration & dosage
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D008024:Ligands; D017447:Receptors, Dopamine D1; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D004298:Dopamine