Molecular Boolean analyses of chemokine (C–C motif) receptor 1, α1B-adrenoceptor and arginine vasopressin receptor 1A heteromers

We reported previously that many chemokine receptors can form heteromeric complexes with α_1B-adrenoceptor (α_1B-AR) and arginine vasopressin receptor 1 A (AVPR1A). To gain initial insight into the relative proportions of receptors that may participate in the formation of such heteromers, we performed molecular Boolean (MolBoolean) analyses of receptor-receptor interactions in an expression system and in primary human aortic vascular smooth muscle cells (hVSMCs), utilizing chemokine (C-C motif) receptor 1, α_1B-adrenoceptor and AVPR1A as representative receptor partners. In HEK293T cells co-expressing all three receptors, 60-70 % of each recombinant receptor were located proximal enough to permit heteromerization with the other two receptor partners. In primary human vascular smooth muscle cells, 30-50 % of each receptor were located proximal enough to permit heteromerization with the other two receptor partners. The MolBoolean analyses of receptor-receptor interactions provides new insights into the spatial distribution of GPCRs in the plasma membrane. Our finding that large proportions of the receptor partners may be able to participate in heteromerization supports the concept that such hetero-oligomeric complexes composed of CCR1, α_1B-AR and AVPR1A could be of physiological relevance.