| In previous years, it was well accepted that G-protein coupled receptors (GPCRs) were synthesized and functioned as a single protomer. However, the availability of new reagents and techniques to study GPCRs have contributed to the general acceptance that GPCRs are synthesized and function as dimers and/or oligomers. GPCR dimers do not only contain two identical receptors subtypes (homodimers), but can also contain two non identical receptors subtypes (heterodimers). Such interactions have been shown to have profound and diverse implications on receptor pharmacology, including ligand binding profiles, signaling, and trafficking. The presence of GPCRs in dimeric/oligomerc complexes may well underlie reported functional interactions between different receptor systems.; We investigated if interactions between opiates and alpha2-adrenergics observed in analgesia responses could be described by interacting opioid and alpha 2A-adrenergic (alpha2A) receptors. We find that both mu and delta opioid receptors can be isolated in interacting complexes with alpha 2A receptors and show that they are in close enough proximity in live cells, such that physical associations can be fostered. In functional assays, we observe that the mere presence of alpha2A receptors in complexes with either mu and delta receptors is sufficient to enhance opiate mediated signaling. In addition we describe that co-activation of both receptors can lead to attenuated signaling responses. Our findings reveal functional interactions between opioid and alpha2A receptors that can be attributed to physical association between these receptor subtypes.; Many studies have supported interactions between opioid and CB1-cannabinoid (CB1) receptors. We observe that all three opioid receptors (mu, delta, kappa) are in close enough proximity to associate with CB1 receptors in live cells using BRET. We focused our attention on interactions between mu and CB1 receptors and observe that whereas the presence of CB1 receptors does not affect mu receptor signaling, co-activation of both receptors causes signaling attenuation.; Taken together, our studies support the notion that physical interactions between opioid and alpha2A as well as between opioid and CB1 receptors may contribute to functional interactions between drugs that act through these receptors. |
