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摘要
beta(1)- and beta(2)-Adrenergic receptors (beta(1)-AR and beta(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 beta(1)-AR, beta(2)-AR, mu opioid receptor and delta opioid receptor, can form homo- and heterooligomers. Previous studies demonstrated that the beta(1)-AR and beta(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 beta(1)-AR and beta(2)-AR. Using co-immunoprecipitation, we confirmed that beta(1)-AR and beta(2)-AR formed heterooligomers in the CHO-K1 cells. In cells co-expressing beta(1)-AR and beta(2)-AR, 30% of beta(1)-AR was internalized by isoproterenol, whereas only 20% of beta(1)-AR was internalized in cells expressing the beta(1)-AR alone. Heterooligomerization did not affect the ratio of internalized beta(2)-AR. Salmeterol, a specific beta(2)-AR agonist, broke beta(1)-AR/beta(2)-AR heterooligomers, and induced beta(2)-AR-specific internalization in cells co-expressing beta(1)-AR and beta(2)-AR. The present study demonstrated that heterooligomerization between beta(1)-AR and beta(2)-AR accelerates the isoproterenol-promoted internalization of the beta(1)-AR, and that salmeterol induces beta(2)-AR-specific internalization in Chinese hamster ovary (CHO) cells stably co-expressing beta(1)-AR and beta(2)-AR.
- 出版日期2013-1
