Beta-blockers show inverse agonism to a novel constitutively active mutant of β1-adrenoceptor

Maruf Ahmed, Habib Abul Muntasir, Murad Hossain, Masaji Ishiguro, Tadazumi Komiyama, Ikunobu Muramatsu, Hitoshi Kurose, Takafumi Nagatomo

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7 Citations (Scopus)

Abstract

We obtained a new mutant of the β1-adrenergic receptor (β1-AR) by point mutations that can constitutively activate β1-AR. Aspartate 104 of the β1-AR in the 2nd transmembrane was replaced with alanine. The β1-AR mutant expressed in human embryonic kidney (HEK)-293 cells displayed high level of constitutive activity with respect to wild-type (P<0.05), which could be partially inhibited by some beta-blockers. The constitutive activity of the mutant was confirmed by the finding that the enhanced activity is dependent on the level of receptor expression. The results of this study might have interesting implications for future studies aiming at elucidating the activation process of the β1-AR as well as the mechanism of action of beta-blockers.

Original languageEnglish
Pages (from-to)167-172
Number of pages6
JournalJournal of Pharmacological Sciences
Volume102
Issue number2
DOIs
Publication statusPublished - Nov 10 2006

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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    Ahmed, M., Muntasir, H. A., Hossain, M., Ishiguro, M., Komiyama, T., Muramatsu, I., Kurose, H., & Nagatomo, T. (2006). Beta-blockers show inverse agonism to a novel constitutively active mutant of β1-adrenoceptor. Journal of Pharmacological Sciences, 102(2), 167-172. https://doi.org/10.1254/jphs.FP0060640