LAUSR

Previously, we reported that chemokine (C‐C motif) receptor 2 (CCR2) heteromerizes with α1B‐adrenoceptor (α1B‐AR) in leukocytes, through which α1B‐AR controls CCR2. Whether such heteromers are expressed in human vascular smooth muscle cells (hVSMCs) is unknown. Bioluminescence resonance energy transfer confirmed formation of recombinant CCR2:α1b‐AR heteromers. Proximity ligation assays detected CCR2:α1B‐AR heteromers in hVSMCs and human mesenteric arteries. CCR2:α1B‐AR heteromerization per se enhanced α1B‐AR‐mediated Gαq‐coupling. Chemokine (C‐C motif) ligand 2 (CCL2) binding to CCR2 inhibited Gαq activation via α1B‐AR, cross‐recruited β‐arrestin to and induced internalization of α1B‐AR in recombinant systems and in hVSMCs. Our findings suggest that CCR2 within CCR2:α1B‐AR heteromers biases α1B‐AR signaling and provide a mechanism for previous observations suggesting a role for CCL2/CCR2 in the regulation of cardiovascular function.