Abstract

The purpose of the present study was to investigate the effects of a Ca antagonist (diltiazem) on dopamine release in the central nervous system. Rat striatal slices prelabeled with [3H]dopamine (DA) and superfused with Krebs-Ringer solution were stimulated electrically at a frequency of 1 Hz. Exposure to diltiazem (3.3 x 10(-7) to 1 x 10(-5) mol/L) significantly increased both the basal and stimulation-evoked [3H]DA release in a dose-dependent manner. Exogenously applied unlabeled DA inhibited the stimulation-evoked [3H]DA release. Diltiazem significantly antagonized the capacity of the unlabeled DA to inhibit stimulation-evoked [3H]DA release. The blockade of D2 receptors by a preferential D2 antagonist, sulpiride, reduced the facilitatory effect of diltiazem on stimulation-evoked [3H]DA release. Pretreatment with pertussis toxin, which interferes with the coupling of the inhibitory guanosine triphosphate-binding proteins to adenylate cyclase, significantly diminished the effects of diltiazem on stimulation-evoked [3H]DA release. These results show that diltiazem increased DA release in rat striatum, at least partially by interactions with the D2 autoreceptors and pertussis toxin-sensitive guanosine triphosphate-binding proteins.

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