Antagonist-mediated down-regulation of 5-hydroxytryptamine type 2 receptor gene expression: modulation of transcription.
Prolonged exposure to an agonist results in a progressive loss of most G protein-coupled receptors, whereas exposure to an antagonist causes increased receptor response. The 5-hydroxytryptamine (5-HT)2 receptor is down-regulated by agonists but, paradoxically, antagonists can also elicit a decrease in receptor density. Here we show that long term treatment with serotonin or mianserin, an antagonist and antidepressant, results in reduced levels of both the 5-HT2 receptor and its RNA. Antagonist-induced down-regulation requires the presence of the 5-HT2 receptor, it occurs at the level of transcription, and it is mediated by a drug response sequence in the 5' flanking region of the 5-HT2 receptor gene. The effect of mianserin might result, at least in part, from its ability to modulate transcription.
Toth
M
M
Howard Hughes Medical Institute, Department of Molecular Biology, Princeton University, New Jersey 08544-1014.
Shenk
T
T
D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation; D005786:Gene Expression Regulation; D008803:Mianserin / Q000494:pharmacology; D012313:RNA / Q000378:metabolism; D051381:Rats; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D008803:Mianserin; D012701:Serotonin; D012313:RNA