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  • Title: Sigma1 receptor agonist-mediated regulation of N-methyl-D-aspartate-stimulated [3H]dopamine release is dependent upon protein kinase C.
    Author: Nuwayhid SJ, Werling LL.
    Journal: J Pharmacol Exp Ther; 2003 Jan; 304(1):364-9. PubMed ID: 12490613.
    Abstract:
    We have previously shown that sigma1 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 sigma1 receptor-selective and nonsubtype-selective sigma receptor antagonists. Based on previous evidence from our laboratory as well as other laboratories, we hypothesized that sigma1 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 sigma1 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 sigma1 receptor agonist (+)-pentazocine in a concentration-related manner. We also found that prior exposure to 1 microM phorbol 2-myristate 13-acetate for 30 min abolished regulation by (+)-pentazocine. We concluded that an intact PKC system was required for sigma1 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
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