Hetero-oligomers of alpha2A-adrenergic and mu-opioid receptors do not lead to transactivation of G-proteins or altered endocytosis profiles.

Complexes of alpha(2A)-ARs (alpha(2A)-adrenergic receptors) and MORs (mu-opioid receptors), probably hetero-oligomers, were detected by co-immunoisolation after extraction from HEK-293 cells (human embryonic kidney 293 cells). Functional communication between these receptors is revealed by alpha(2A)-AR activation of a pertussis toxin-insensitive G(i)alpha subunit (termed as G(i)1) when fused with the MOR and evaluated in membranes from pertussis toxin-treated cells. However, the alpha(2A)-AR does not require transactivation through MOR, since quantitatively indistinguishable results were observed in cells co-expressing alpha(2A)-AR and a fusion protein of G(i)1 with the first transmembrane span of MOR (myc-MOR-TM1). Functional cross-talk among these alpha(2A)-AR-MOR complexes does not occur for internalization profiles; incubation with adrenaline (epinephrine) leads to endocytosis of alpha(2A)-AR but not MOR, while incubation with DAMGO ([D-Ala,NMe-Phe,Gly-ol]enkephalin) leads to endocytosis of MOR but not alpha(2A)-AR in cells co-expressing both the receptors. Hence, alpha(2A)-AR and MOR hetero-oligomers, although they occur, do not have an obligatory functional influence on one another in the paradigms studied.