
<ArticleTitle><prot>Protein kinase C</prot> regulates <prot>dopamine D4 receptor</prot>-mediated phospholipid methylation.</ArticleTitle>
<AbstractText><prot>Dopamine D4 receptors</prot> (<prot>D4 receptors</prot>) mediate dopamine-stimulated, folate-dependent phospholipid methylation. To investigate possible regulation of this multi-step D4 receptor-mediated phospholipid methylation cycle by protein kinases, specific kinase activators and inhibitors were studied in SK-N-MC human neuroblastoma cells, using [14C] formate to label folate-derived single-carbon groups. Phorbol dibutyrate (PDB), an activator of <prot>protein kinase C</prot>, stimulated basal phospholipid methylation and also shifted the dose-response curve for dopamine-stimulated phospholipid methylation to the right by more than an order of magnitude. <prot>Calphostin C</prot>, an <prot>inhibitor of <prot>protein kinase C</prot></prot>, had little effect on basal phospholipid methylation but significantly inhibited dopamine-stimulated phospholipid methylation and also blocked the stimulatory response to PDB. Chelerythrine, which inhibits <prot>protein kinase C</prot> and other kinases, strongly inhibited both basal and dopamine-stimulated phospholipid methylation. Forskolin, an activator of <prot>protein kinase A</prot>, inhibited basal and dopamine-stimulated phospholipid methylation, but only at high concentrations while Rp-cAMP, an inhibitor of <prot>protein kinase A</prot>, did not block this effect. Inhibition of <prot>protein kinase G</prot> produced a modest decrease in dopamine-stimulated phospholipid methylation, but neither sodium nitroprusside, which increases nitric oxide (NO) production and activates <prot>protein kinase G</prot>, nor the <prot>NO synthase</prot> inhibitor N-nitro-L-arginine had any effect on basal or dopamine-stimulated phospholipid methylation. These observations indicate that <prot>protein kinase C</prot> is an important regulator of basal and D4 receptor-mediated folate-dependent phospholipid methylation, whereas <prot>protein kinase A</prot> and <prot>protein kinase G</prot> have a lesser or minimal role.</AbstractText>
