ς1 Receptor Agonist-Mediated Regulation of N-Methyl-d-aspartate-Stimulated [3H]Dopamine Release Is Dependent upon Protein Kinase C

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Abstract
We have previously shown that ς1 receptor agonists inhibit N-methyl-d-aspartate (NMDA)-stimulated [3H]dopamine from slices of rat striatum in a concentration-related manner and that the inhibition is reversed by ς1 receptor-selective and nonsubtype-selective ς receptor antagonists. Based on previous evidence from our laboratory as well as other laboratories, we hypothesized that ς1 receptors might use a protein kinase C (PKC) signaling pathway to modulate stimulated dopamine release. We tested several inhibitors of PKC isozymes, as well as a phospholipase C inhibitor for their effects on ς1 receptor agonist-mediated regulation of [3H]dopamine release. Although none of the inhibitors tested affected the ability of NMDA to stimulate [3H]dopamine release, they all abolished regulation by the ς1 receptor agonist (+)-pentazocine in a concentration-related manner. We also found that prior exposure to 1 μM phorbol 2-myristate 13-acetate for 30 min abolished regulation by (+)-pentazocine. We concluded that an intact PKC system was required for ς1 agonist-mediated regulation of NMDA-stimulated [3H]dopamine release from rat striatal slices. Based on the pharmacological profile of the PKC inhibitors tested, as well as reports in the literature on PKC involvement in neurotransmitter release and ς receptor action, PKCβ seems most likely to be responsible, at least in part, for the effects of (+)-pentazocine on dopamine release.

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