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Guinea pig hippocampal 5‐HT1E receptors: a tool for selective drug development
Author(s) -
Klein Michael Thomas,
Smith Carol,
Toohey Nicole,
Teitler Milt
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.720.8
Subject(s) - guinea pig , ritanserin , receptor , 5 ht receptor , hippocampal formation , pharmacology , chemistry , hippocampus , serotonin , biology , endocrinology , biochemistry
Recent studies have indicated that the 5‐HT 1E R, discovered in human brain tissue (Leonhardt et al, 1989), is not expressed in mouse or rat brain, but is expressed in guinea pig brain (Bai et al, 2004). Thus there have been few reports on 5‐HT 1E R drug development. In order to establish an animal model that will allow 5‐HT 1E R drug development we identified regions of the guinea pig brain that when homogenized exhibit 5‐CT, mesulergine, and sumatriptan ‐insensitive 3 H5‐HT binding (characteristic of the 5‐HT 1E R). The hippocampus was determined to have a receptor density sufficiently high for further analysis. In hippocampal homogenates, 100nM 5‐CT, 30nM ritanserin, and 100nM LY344864 were used to block high‐affinity 3 H5‐HT binding at non‐1E binding sites. The Kd value of 3 H5‐HT was found to be 5.7±0.7nM which is indistinguishable from the cloned receptor Kd of 5.7±0.6nM. Drug affinities for the hippocampal and cloned 5‐HT 1E R binding were identical. These findings indicate the 3 H‐5‐HT binding is specific to the guinea pig 5‐HT 1E R and levels of receptors can be determined in various brain tissues. Autoradiographical analysis and signal transduction studies of 5‐HT 1E R in guinea pig brain can thus be determined. This should provide important insights into possible functions of the 5‐HT 1E R receptor and may predict the possible therapeutic potential of selective h5‐HT 1E R agonists and antagonists. (Supported by MH56650)