Transmitter-like release of endogenous DOPA and regulatory actions of L-DOPA on the release of dopamine via presynaptic receptors in rat striatal and hypothalamic slices.

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DOPA, a precursor of dopamine (DA), has been generally accepted to act through its conversion to DA by DOPA-decarboxylase. However, depolarization released endogenous DOPA from superfused slices of rat striata. We compared the characteristics of the DOPA release with those of DA and also studied actions of exogenously applied DOPA on the release of DA and norepinephrine (NE).1. Electrical field stimulation with biphasic impulses (2 Hz) released DOPA and DA via a terodo toxin-sensitive and Ca^<2+>-dependent process. High K^+ 715 mM) also released DOPA and DA via a Ca^<2+> dependent process. In slices superfused with ^3H-tyrosine (1 <micro>M)-containing medium, high K^+ (15 and 60 mM) released DOPA and DA with a concentration-dependent decrease in tyrosine hydroxylase activity, ^3H-H_2O formation, followed by a concentration-dependent increase after the release of DA ended. DOPA appears to be released by an excitation-secretion coupling process.2. In striatal alices, DOPA 30 nM facilitated the evoked release of DA without increases in the sponyaneous release and tissue content of DA. In the presence of NSD-1055, a DOPA-decarboxylase inhi bitor, DOPA 10 nM to 1 <micro>M produces biphasic actions on the evoked release of DA, facilitation at 30 nM via presynaptic <beta>-adrenoceptors and inhibition at 1 <micrn>M via presynaptic DA receptor Similar biphasic actions of DOPA on the release of DA and NE were also seen in rat hypothalamic slices.A transmitter-like release of DOPA was seen in rat striatal slices. Biphasic regulatory actions of DOPA itself on the release of DA and NE seen in rat striatal and hypothalamic slices. These findings support a working hypothesis that DOPA plays a role as a neuroactive substance in these brain regions.