Role of nerve terminal L-type Ca2+ channel in the brain.
The microinjection of Bay K 8644 (BAYK), an L-type Ca2+ channel stimulant, into rat caudate putamen dose-dependently potentiated locomotor activity. DA receptor antagonists significantly blocked BAYK-induced hyperactivity. Striatal DA levels as detected by microdialysis increased 140 fold above steady state levels 20 min after BAYK administration into caudate putamen. This increase was not influenced by a Na+ channel blocker. Pretreatment with 1,4-dihydropyridine (DHP) L-type Ca2+ channel antagonists, but not nifedipine, into caudate putamen significantly blocked the BAYK induced-hyperactivity and DA efflux. The lowest level of intracellular DA detected by fluorohistochemistry coincided with the highest level of extracellular DA. These results indicate that the extraordinary DA release is regulated by a subtype of L-type Ca2+ channel that is present in the nerve terminal.
Watanabe
Y
Y
Department of Pharmacology, Tokyo Medical College, Japan.
Lawlor
G F
GF
Fujiwara
M
M
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002421:Caudate Nucleus / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D009411:Nerve Endings / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D011699:Putamen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D004298:Dopamine