Stimulation of [35S]GTPγS binding by 14-methoxymetopon and DAMGO Stimulation of [35S]GTPγS binding was performed in cell membranes isolated from CHO cells stably transfected with the indicated murine MOR-1 splice variant. EC50 and maximal stimulation data (normalized to the percentage of stimulation of 10 μM DAMGO) was computed using GraphPad Prism. Values represent the mean ± S.E.M. for at least three independent experiments. Two-way analysis of variance followed by Bonferroni's post-tests showed a significant difference between the EC50 of 14-methoxymetopon and DAMGO for MOR-1 (p < 0.001), MOR-1A (p < 0.001), MOR-1B (p < 0.01), MOR-1C (p < 0.05), and MOR-1F (p < 0.001). 14-Methoxymetopon is significantly more efficacious than DAMGO for MOR-1C (p < 0.001).
14-Methoxymetopon | DAMGO | Relative Activity of 14-Methoxymetopon | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EC50 | Maximal Stimulation | EC50/KD Ratio | EC50 | Maximal Stimulation | EC50/KD Ratio | EC50 | EC50/KD Ratio | ||||||
| nM | % DAMGO | nM | % DAMGO | ||||||||||
| MOR-1 | 1.1 ± 0.5 | 125.1 ± 4.9 | 6.9 | 55.5 ± 22.2 | 105 ± 6 | 142 | 51 | 21 | |||||
| MOR-1A | 4.5 ± 1.9 | 99.0 ± 6.5 | 16.7 | 74.1 ± 13.9 | 99.2 ± 0.1 | 114 | 17 | 6.8 | |||||
| MOR-1B1 | 1.6 ± 0.3 | 92.3 ± 3.6 | 7.6 | 52.3 ± 29.9 | 97.9 ± 1.5 | 109 | 33 | 14 | |||||
| MOR-1C | 4.2 ± 0.9 | 125 ± 25 | 42 | 42.5 ± 26.4 | 98.1 ± 7.0 | 48 | 10 | 1.2 | |||||
| MOR-1D | 1.1 ± 0.2 | 101.7 ± 8.4 | 5.8 | 17.8 ± 5.4 | 96.6 ± 1.6 | 19.6 | 16 | 3.4 | |||||
| MOR-1E | 0.5 ± 0.1 | 109 ± 12 | 2.5 | 32.4 ± 10.4 | 95.7 ± 4.1 | 30.9 | 65 | 12 | |||||
| MOR-1F | 2.7 ± 0.3 | 117 ± 14 | 2.3 | 67.6 ± 31.2 | 99.2 ± 0.4 | 96.6 | 25 | 42 | |||||