Inhibition of forskolin-stimulated cAMP accumulation by opioids in hMOR-1 variants^a.

aThe IC50 and maximal inhibition were calculated by nonlinear regression analysis using Prism 4.0, GraphPad Software. Results are means ± S.E.M. of 3–7 independent determinations. Maximal inhibition: Maximal inhibition was determined after correcting for different receptor expression levels by western blot analyses (Figure S3). The expression levels of receptor variants were calculated relative to that of hMOR-1 (which was set to 1). Significant differences in maximal inhibition were observed for DAMGO (p<0.05), morphine (p<0.01) and M6G (p<0.01). For maximal inhibition by DAMGO, post hoc Tukey analyses showed that hMOR-1 differed from hMOR-1A (p<0.05). For maximal inhibition by morphine, post hoc Tukey analysis showed that hMOR-1 differed from hMOR-1A2 (p<0.01) and hMOR-1A (p<0.05). For maximal inhibition by M6G, post hoc Tukey analysis showed that hMOR-1 differed from hMOR-1A2 (p<0.05) and hMOR-1A (p<0.05). IC50: Significant differences of IC50 were observed for DAMGO (p<0.0001), morphine (p<0.05) and M6G (p<0.05). For DAMGO, post hoc Tukey analyses showed that the IC50 value of hMOR-1 differed from hMOR-1A2 (p<0.001), and hMOR-1A2 differed also from hMOR-1A (p<0.001) and hMOR-1Y2 (p<0.001). For morphine, post hoc Tukey analyses showed that the IC50 value of hMOR-1 differed from hMOR-1A2 (p<0.05). For M6G, post hoc Tukey analyses showed that the IC50 value of hMOR-1 differed from hMOR-1A2 (p<0.05) and hMOR-1A2 differed also from hMOR-1A (p<0.05) and hMOR-1Y2 (p<0.05). ND: not determinable.