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.

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