TY - JOUR T1 - Antagonist-mediated down-regulation of 5-hydroxytryptamine type 2 receptor gene expression: modulation of transcription. JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1095 LP - 1100 VL - 45 IS - 6 AU - M Toth AU - T Shenk Y1 - 1994/06/01 UR - http://molpharm.aspetjournals.org/content/45/6/1095.abstract N2 - 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. ER -