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