Regarding the binding affinities of exogenous ligands, including DAMGO, morphine, morphine-6-glucuronide, CTOP, diprenorphine and/or naloxone, there were no differences observed between G118/D40- and A118/N40-hMOPR expressed in cell lines such as AV-2 [4,38], COS [40] and HEK293 [37] cells, or between G112/D38-MOPR and A112/N38-MOPR in G/G and A/A mice, respectively [18]. Although G118/D40-hMOPR expressed in AV-12 cells was initially reported to have three times higher binding affinity of β-endorphin, an endogenous ligand, than A118/N40-hMOPR [4], this finding was not reproduced in two studies using COS [40] and HEK293 [37] cells. Furthermore, MOPRs in the brains of G/G and A/A mice [18] or G118-h/mMOPR and A118-h/mMOPR expressed in CHO cells [19] did not differ in their binding affinity for β-endorphin. In addition, G118/D40- and A118/N40-hMOPR expressed in COS cells had similar binding affinities for other endogenous opioids, including met-enkephalin and dynorphin A [40]. Therefore, A118G SNP alters N-glycosylation of the MOPR in the N-terminal domain without changing its ligand binding affinities. This is not unexpected as the ligand binding pocket of the MOPR has been proposed to be formed mainly by amino acids in its transmembrane domains and, to much lower extents, extracellular domains [42,43].
