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Specificity of 5‐HT2A Receptor Ligands in Mice
Author(s) -
Silva Uade Olaghere da,
SandersBush Elaine
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1125.3
Subject(s) - receptor , in vivo , serotonin , antagonist , pharmacology , gene isoform , receptor antagonist , 5 ht receptor , chemistry , in vitro , ligand (biochemistry) , biochemistry , biology , gene , microbiology and biotechnology
In‐Vitro studies of RNA editing of the serotonin type 2C receptor (5‐HT2CR) have shown a pronounced loss of function in the fully edited isoform (VGV). Our goal is to evaluate functional coupling of the edited 5‐HT2CR in‐vivo using transgenic mice that solely express the VGV isoform. In order to accomplish this goal, we must be able to establish selective activation of the receptor both in‐vitro and in‐vivo. This makes ligand specificity of the utmost importance. Since pharmacological studies are not available for mice, we compared the relative affinity of antagonists for 5‐HT2A versus 5‐HT2C receptors, confirming that M100907 and SB206553 were relatively selective. In order to examine receptor specificity in‐vivo, N‐ethoxycarbonyl‐2‐ethoxy‐1,2‐dihydroquinoline (EEDQ), an irreversible alkylating agent, was injected i.p. to inactivate sites in frontal cortex. We then tested the ability of pretreatment with antagonists to block EEDQ. While 0.25 mg/kg of the 5‐HT2A antagonist M100907 prevented 5‐HT2A inactivation, it did not protect 5HT2C sites. In contrast, the 5HT 2C antagonist SB206553 did not protect 5‐HT2A receptors. (Supported by NIH grants T32MH065782 and R01MH34007)