Characterization of vinpocetine effects on DA and DOPAC release in striatal isolated nerve endings

The effect of vinpocetine, a nootropic drug with anti-ischemic potential, o n the release of DA and its main metabolite, DOPAC, was investigated in str iatum isolated nerve endings under resting and depolarized conditions. Vinp ocetine does not modify the baseline release of DA or the exocytotic releas e of DA evoked by high K+, but inhibits the release of DA evoked by veratri dine reversal of the DA transporter. In addition to these results, which co nfirm the vinpocetine selective blockade of voltage-sensitive presynaptic N a channels (VSSC) previously reported [Neurochem. Res. 24 (1999) 1585], vin pocetine increases DOPAC release either under resting, veratridine or high K+ depolarized conditions. This latter effect, which does not involve VSSC, was characterized. The parallel determination of the released and retained catecholamine concentrations revealed that vinpocetine increases DOPAC rel ease at the expense of internal DA in a dose-dependent manner (low LM range ). In contrast to vinpocetine, the selective MAO-A inhibitor, clorgyline, i ncreases DA and decreases DOPAC formation. The combined action of vinpoceti ne and clorgyline does not indicate, however, that the activation of MAO is the mechanism responsible for the increase in DOPAC caused by vinpocetine. Reserpine, although more potent and efficient than vinpocetine, qualitativ ely exerts the same pattern of changes on DA and DOPAC concentrations. It i s concluded that, in addition to the inhibition of presynaptic VSSC permeab ility, which selectively inhibits the transporter-mediated release of all n eurotransmitters, vinpocetine increases DOPAC by impairing the vesicular st orage of DA. Our results indicate that the cytoplasm extravesicular DA is m etabolized by MAO to DOPAC. Most of the DOPAC formed is exported to the ext racellular medium. (C) 2001 Elsevier Science B.V. All rights reserved.