The role of protein kinase C in the regulation of serotonin-2A receptor expression

Antje Anji, Nicole R. Sullivan Hanley, Meena Kumari, Julie G. Hensler

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

We have investigated in C6 glioma cells the involvement of protein kinase C (PKC) in the regulation of serotonin-2A receptor (5-HT2A receptor) expression by agonist treatment. Comparison of the time-courses of agonist-induced down-regulation of receptor number and mRNA indicate that a decrease in the number of 5-HT2A receptor binding sites in response to serotonin (5-HT) treatment is preceded by a decrease in 5-HT2A receptor mRNA. This decrease in 5-HT2A receptor mRNA as a result of agonist exposure was not due to a change in the stability or half-life of the transcript. Pretreatment of cells with the PKC inhibitor bisindolyl-maleimide blocked the decrease in 5-HT2A receptor mRNA levels, and attenuated the down-regulation of 5-HT2A receptor binding sites induced by treatment with 5-HT. Experiments performed with the PKC inhibitors calphostin C and Gö 6976 confirmed that PKC was involved in the regulation of 5-HT2A receptor mRNA by agonist and implicate the conventional subgroup of PKC isoforms. Western blot analysis, using isoform-specific anti-PKC antibodies showed that under our culture conditions C6 glioma cells express the conventional isoforms PKC α, PKC γ, as well as the novel isoforms PKC δ, PKC ε, and the atypical isoforms PKC λ and PKC ι. Upon treatment with 5-HT for 10 min levels of the conventional isoforms PKC α and PKC γ increased in the nuclear fraction. Taken together, our results implicate PKC α and/or PKC γ in the regulation of 5-HT2A mRNA receptor and binding sites in response to agonist treatment.

Original languageEnglish (US)
Pages (from-to)589-597
Number of pages9
JournalJournal of neurochemistry
Volume77
Issue number2
DOIs
StatePublished - 2001

Keywords

  • 5-HT receptor
  • Protein kinase C isoforms
  • Receptor down-regulation
  • mRNA

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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