Effects of spinophilin on the function of RGS8 regulating signals from M2 and M3-mAChRs.

We found that a scaffold protein, spinophilin (SPL), can interact with M2 and M3-muscarinic acetylcholine receptors (mAChRs). As SPL can also bind to RGS8 by using the different region of SPL, we investigated the effects of SPL on the function of RGS8 regulating signals from M2 and M3 receptors. M2 receptor-mediated Gi-signaling was studied by monitoring G-protein-coupled inwardly rectifying K+ channels, and M3 receptor-mediated Gq-signaling was monitored by the increase of Ca2+-activated Cl(-) current. The expression of SPL could enhance the regulatory function of RGS8 on the M3-mAChR, but the acceleration function of RGS8 on the M2-mediated signaling could not be enhanced by SPL. Results showed that the recruitment of RGS8 to the receptor differentially affects the function of RGS8 among receptors.