Modulation of dopamine release from rat striatum by protein kinase C: interaction with presynaptic D2-dopamine-autoreceptors

British Journal of Pharmacology
L IannazzoH Majewski

Abstract

1. Interactions between dopamine receptors and protein kinase C (PKC) have been proposed from biochemical studies. The aim of the present study was to investigate the hypothesis that there is an interaction between protein kinase C and inhibitory D2-dopamine receptors in the modulation of stimulation-induced (S-I) dopamine release from rat striatal slices incubated with [3H]-dopamine. Dopamine release can be modulated by protein kinase C and inhibitory presynaptic D2 receptors since phorbol dibutyrate (PDB) and (-)-sulpiride, respectively, elevated S-I dopamine release. 2. The protein kinase C inhibitors polymyxin B (21 microM) and chelerythrine (3 microM) had no effect on stimulation-induced (S-I) dopamine release. However, when presynaptic dopamine D2 receptors were blocked by sulpiride (1 microM), an inhibitory effect of both PKC inhibitors on S-I dopamine release was revealed. Thus, sulpiride unmasks an endogenous PKC effect on dopamine release which suggests that presynaptic D2 receptors normally suppress endogenous PKC activity. This is supported by results in striatal slices which were pretreated with PDB to down-regulate PKC. In this case the facilitatory effect of sulpiride was completely abolished. 3. The inhibitory e...Continue Reading

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Citations

Aug 11, 2000·European Journal of Pharmacology·T L ThompsonB Smith
Jul 22, 1998·Progress in Neurobiology·H Majewski, L Iannazzo
Dec 3, 2014·Neuropharmacology·Kathryn D LudermanMargaret E Gnegy
Sep 27, 2003·Journal of Neurochemistry·Yvonne SchmitzDavid Sulzer
Mar 22, 2002·The European Journal of Neuroscience·Alessandro StefaniGiorgio Bernardi
Oct 15, 2019·Synapse·Gabriel López-RamírezBenjamín Florán

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