title: Clozapine downregulates 5-hydroxytryptamine6 (5-HT6) and upregulates 5-HT7 receptors in HeLa cells.
abstract: Clozapine is an atypical antipsychotic with high affinity for several serotonin receptors. This drug causes paradoxical downregulation of 5-hydroxytryptamine(2A) (5-HT)(2A) receptors, but its modulation of other serotonin receptors has not been studied. We examined the effects of clozapine and several other drugs on the regulation of rat 5-HT(6) and 5-HT(7) receptors individually expressed in transfected HeLa cells. Both 5-HT(6) and 5-HT(7) receptor densities (B(max)) were reduced by 5-carboxamidotryptamine, an agonist, and methiothepin, an inverse agonist. Clozapine reduced 5-HT(6) B(max). This suggests that 5-HT(6) receptors are also paradoxically downregulated by the antagonist clozapine. 5-Hydroxytryptamine(7) receptor B(max), on the other hand, was increased by clozapine. Clozapine's modulation of the 5-HT(6) and 5-HT(7) receptor levels may be important in the action of this atypical antipsychotic.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Harborview Medical Center, University of Washington, Box 359911, 325 Ninth Avenue, Seattle, WA 98195, USA.
authors.forename: N L
authors.initials: NL
authors.lastname: Zhukovskaya
authors.forename: J F
authors.initials: JF
authors.lastname: Neumaier
mesh_terms: D000818:Animals; D003024:Clozapine / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D006367:HeLa Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D008719:Methiothepin / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000096:biosynthesis*; D012701:Serotonin / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C104425:serotonin 7 receptor; D012701:Serotonin; D008719:Methiothepin; C047087:5-carboxamidotryptamine; D003024:Clozapine