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β(1)- and β(2)-Adrenergic receptors (β(1)-AR and β(2)-AR) are co-expressed in numerous tissues, for example, heart and bladder. They play a very important role in the responses of a variety of organs to sympathetic nerve stimulation. Recent studies suggest that many G protein-coupled receptors, such as β(1)-AR, β(2)-AR, μ opioid receptor and δ opioid receptor, can form homo- and heterooligomers. Previous studies demonstrated that the β(1)-AR and β(2)-AR formed dimers in living HEK 293 cells. The aim of the present study is to investigate whether such heterooligomerization affect the agonist-induced receptor internalization in the CHO-K1 cells stably co-expressing β(1)-AR and β(2)-AR. Using co-immunoprecipitation, we confirmed that β(1)-AR and β(2)-AR formed heterooligomers in the CHO-K1 cells. In cells co-expressing β(1)-AR and β(2)-AR, 30% of β(1)-AR was internalized by isoproterenol, whereas only 20% of β(1)-AR was internalized in cells expressing the β(1)-AR alone. Heterooligomerization did not affect the ratio of internalized β(2)-AR. Salmeterol, a specific β(2)-AR agonist, broke β(1)-AR/β(2)-AR heterooligomers, and induced β(2)-AR-specific internalization in cells co-expressing β(1)-AR and β(2)-AR. The present study demonstrated that heterooligomerization between β(1)-AR and β(2)-AR accelerates the isoproterenol-promoted internalization of the β(1)-AR, and that salmeterol induces β(2)-AR-specific internalization in Chinese hamster ovary (CHO) cells stably co-expressing β(1)-AR and β(2)-AR.


Takako Yoshihara, Yuzuru Yonoki, Maki Saito, Tsutomu Nakahara, Kenji Sakamoto, Kunio Ishii. Agonist-induced receptor internalization in Chinese hamster ovary cells stably co-expressing β(1)- and β(2)-adrenergic receptors. Biological & pharmaceutical bulletin. 2013;36(1):114-9

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PMID: 23302644

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