Identification of a Key Amino Acid of the Human 5-HT2B Serotonin Receptor Important for Sarpogrelate Binding

Journal of Pharmacological Sciences

Habib Abul Muntasir¹  Murad Hossain¹  Tadazumi Komiyama³  Takafumi Nagatomo¹  Takashi Nakamura¹  Masanobu Ozaki²  Mohiuddin Ahmed Bhuiyan¹ 

[1] Department of Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Japan;Department of Fundamental Pharmacology & Therapeutics, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Japan;Department of Biochemistry, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Japan

关键词: 5-HT2B receptor;    sarpogrelate;    site-directed mutagenesis;   

DOI  :  10.1254/jphs.SC0060241

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(15)Cited-By(5)Based on radio-ligand binding and molecular modeling studies, sarpogrelate shows a moderate selectivity for 5-HT2B versus 5-HT2A receptors. To confirm the modeling data of sarpogrelate to 5-HT2B receptors predicting interaction of sarpogrelate towards Asp135 in helix 3 of 5-HT2B receptors, we constructed and characterized the mutation of this residue by site-directed mutagenesis. The Asp135Ala mutant did not exhibit any affinity for [3H]rauwolscine. Therefore, it was not possible to find sarpogrelate affinity to the mutant using [3H]rauwolscine. The mutation also abolished agonist-stimulated inositol phosphates formation. These results provide evidence that Asp135 is important for the interaction between 5-HT2B receptors and sarpogrelate.

【 授权许可】

Unknown