Most studies to date have examined the functional consequences of this SNP in vitro using various cell culture systems. Initial studies identified an elevated binding affinity of β-endorphin, but not exogenous ligands, in the G118 variant to 3-fold higher than that of the A118 in AV-12 cells stably expressing the human MOPR (hMOPR) variants (Bond et al., 1998). Additionally, β-endorphin was found to be three times more potent in activating GIRK channels in Xenopus oocytes injected with in vitro transcribed mRNAs for the A118 or G118 variants (Bond et al., 1998). Together, these data suggested a gain-of-function of the MOPR as a consequence of the A118G point mutation. However, subsequent studies using other cell culture systems – COS cells (Simian fibroblasts) (Befort et al., 2001) or HEK 293 cells (Human embryonic kidney) (Beyer et al., 2004) – were less conclusive with regard to this altered function of the G118 allele. Another consequence of MOPR activation, Ca2+ inhibition, was investigated using rat sympathetic superior ganglion (SCG) neurons expressing either the A118 or G118 variant of the hMOPR. In these studies, the
