| RRC ID |
6544
|
| 著者 |
Muntasir HA, Hossain M, Bhuiyan MA, Komiyama T, Nakamura T, Ozaki M, Nagatomo T.
|
| タイトル |
Identification of a key amino acid of the human 5-HT(2B) serotonin receptor important for sarpogrelate binding.
|
| ジャーナル |
J Pharmacol Sci
|
| Abstract |
Based on radio-ligand binding and molecular modeling studies, sarpogrelate shows a moderate selectivity for 5-HT(2B) versus 5-HT(2A) receptors. To confirm the modeling data of sarpogrelate to 5-HT(2B) receptors predicting interaction of sarpogrelate towards Asp135 in helix 3 of 5-HT(2B) receptors, we constructed and characterized the mutation of this residue by site-directed mutagenesis. The Asp135Ala mutant did not exhibit any affinity for [(3)H]rauwolscine. Therefore, it was not possible to find sarpogrelate affinity to the mutant using [(3)H]rauwolscine. The mutation also abolished agonist-stimulated inositol phosphates formation. These results provide evidence that Asp135 is important for the interaction between 5-HT(2B) receptors and sarpogrelate.
|
| 巻・号 |
104(3)
|
| ページ |
274-7
|
| 公開日 |
2007-7-1
|
| DOI |
10.1254/jphs.sc0060241
|
| PII |
JST.JSTAGE/jphs/SC0060241
|
| PMID |
17609583
|
| MeSH |
Amino Acids / metabolism*
Blotting, Western
Cell Line
Cells, Cultured
Cyproheptadine / pharmacology
Humans
Indoles / pharmacology
Inositol Phosphates / metabolism
Mutagenesis, Site-Directed
Pyridines / pharmacology
Radioligand Assay
Receptor, Serotonin, 5-HT2B / drug effects*
Receptor, Serotonin, 5-HT2B / genetics
Serotonin Antagonists / metabolism*
Succinates / metabolism*
Yohimbine / metabolism
|
| IF |
2.835
|
| 引用数 |
7
|
| リソース情報 |
| ヒト・動物細胞 |
|
