Effects of Ca2+ channel antagonists on striatal dopamine and DOPA release, studied by in vivo microdialysis

Abstract

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, ω‐conotoxin GVIA, a P‐type Ca²⁺ channel antagonist, ω‐agatoxin IVA, and a Q‐type Ca₂₊ channel antagonist, ω‐conotoxin MVIIC, on the basal and Ca²⁺‐ and K⁺‐evoked release of striatal dopamine and DOPA, by use of in vivo microdialysis. 2 ω‐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 ω‐agatoxin IVA nor ω‐conotoxin MVIIC affected the basal striatal release of dopamine and DOPA. 3 ω‐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 ω‐agatoxin IVA nor ω‐conotoxin MVIIC affected the Ca²⁺‐evoked release of striatal dopamine and DOPA. 4 Both ω‐agatoxin IVA and ω‐conotoxin MVIIC inhibited the K⁺‐evoked release of striatal dopamine (IC₅₀ of ω‐agatoxin IVA=2.65 nM; IC₅₀ of ω‐conotoxin MVIIC=12.54 nM) and DOPA (IC₅₀ of ω‐agatoxin IVA=0.15 nM; IC₅₀ of ω‐conotoxin MVIIC=3.05 nM), whereas ω‐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. British Journal of Pharmacology (1998) 123, 805–814; doi:10.1038/sj.bjp.0701675