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The role of protein kinase C in the regulation of serotonin‐2A receptor expression
Author(s) -
Anji Antje,
Hanley Nicole R. Sullivan,
Kumari Meena,
Hensler Julie G.
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00261.x
Subject(s) - protein kinase c , agonist , gene isoform , receptor , bisindolylmaleimide , microbiology and biotechnology , biology , downregulation and upregulation , endocrinology , medicine , signal transduction , biochemistry , gene
We have investigated in C6 glioma cells the involvement of protein kinase C (PKC) in the regulation of serotonin‐ 2A receptor (5‐HT 2A receptor) expression by agonist treatment. Comparison of the time‐courses of agonist‐induced downregulation of receptor number and mRNA indicate that a decrease in the number of 5‐HT 2A receptor binding sites in response to serotonin (5‐HT) treatment is preceded by a decrease in 5‐HT 2A receptor mRNA. This decrease in 5‐HT 2A 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 bisindolylmaleimide blocked the decrease in 5‐HT 2A receptor mRNA levels, and attenuated the down‐regulation of 5‐HT 2A 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‐HT 2A 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‐HT 2A mRNA receptor and binding sites in response to agonist treatment.