Regulation of mRNA encoding 5-HT2A receptors in P11 cells through a post-transcriptional mechanism requiring activation of protein kinase C

• Published in: The Journal of biological chemistry Vol. 269; no. 50; pp. 31850 - 31857
• Main Authors: Ferry, R C, Unsworth, C D, Artymyshyn, R P, Molinoff, P B
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.12.1994; American Society for Biochemistry and Molecular Biology
• Subjects: Amino Acid Isomerases - genetics; Amphetamines - pharmacology; Animals; Base Sequence; Carrier Proteins - genetics; Cell Line; Cycloheximide - pharmacology; DNA Primers - chemistry; Down-Regulation - drug effects; Enzyme Activation; Gene Expression Regulation - drug effects; In Vitro Techniques; Lysergic Acid Diethylamide - pharmacology; Molecular Sequence Data; Norepinephrine - analogs & derivatives; Norepinephrine - pharmacology; Peptidylprolyl Isomerase; Pituitary Gland; Protein Kinase C - physiology; Rats; Receptors, Serotonin - genetics; RNA Processing, Post-Transcriptional; RNA, Messenger - genetics; Serotonin - pharmacology; Transcription, Genetic
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)31773-3

Exposure of P11 cells to serotonin (5-HT) resulted in a transient increase in levels of 5-HT2A receptor mRNA. Exposure to 5-HT for as short a time as 1 min was sufficient to trigger a delayed increase in receptor mRNA. 5-HT-induced increases in receptor mRNA levels were not antagonized by the protein synthesis inhibitor cycloheximide. The increase in receptor mRNA levels was accompanied by a transient increase in the half-life of receptor mRNA; the rate of transcription of receptor mRNA was unchanged. Submaximal stimulation of phosphinositide hydrolysis by partial agonists or 6-fluoronorepinephrine, an alpha 1-adrenergic receptor agonist, also increased receptor mRNA levels. Exposure to phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, mimicked these effects, whereas the protein kinase C inhibitor bisindolylmaleimide antagonized the effects of both 5-HT and PMA. When agonist-promoted increases in receptor mRNA were prevented, the rate of agonist-induced down-regulation was accelerated. These data suggest that levels of 5-HT2A receptor mRNA are regulated by phospholipase C-coupled receptors via a protein kinase C-dependent, post-transcriptional mechanism and indicate that agonist-promoted increases in levels of 5-HT2A receptor mRNA modulate receptor expression.