Table 1
Affinity (K i, nM) and potency (ED50, nM) of nociceptin, [Tyr1]nociceptin, and dynorphin A at KOR1 receptor chimeras containing e2 loop of KOR1 receptor
| Nociceptin | [Tyr1]Nociceptin | Dynorphin A | |||||
|---|---|---|---|---|---|---|---|
| Ki | ED50 | Ki | ED50 | Ki | ED50 | ||
| KOR1 (K) | 107 ± 12 (4) | >10000 | 3.4 ± 0.2 (4) | 865 ± 3 (3) | 0.10 ± 0.01 (3) | 0.4 ± 0.1 (4) | |
| O[Nt]-K | 73 ± 17 (4) | >10000 | 7.2 ± 1.6 (4) | 258 ± 70 (4) | 0.20 ± 0.06 (3) | 0.9 ± 0.1 (3) | |
| O[tm1-2]-K | 126 ± 20 (3) | >10000 | 6.6 ± 1.2 (3) | 543 ± 15 (2) | 0.06 ± 0.00 (4) | 1.0 ± 0.5 (2) | |
| O[Nt-tm2]-K | 27 ± 1 (3) | >10000 | 1.7 ± 0.4 (3) | 285 ± 45 (2) | 0.07 ± 0.01 (3) | 1.1 ± 0.2 (3) | |
| O[e1]-K | 23 ± 6 (4) | >1000 | 0.12 ± 0.01 (3) | 3.3 ± 0.3 (3) | 0.24 ± 0.04 (4) | 0.3 ± 0.1 (3) | |
| O[Nt, e1]-K | 13 ± 4 (4) | >1000 | 0.07 ± 0.01 (3) | 12 ± 2 (3) | 0.23 ± 0.01 (3) | 0.8 ± 0.5 (3) | |
| O[Nt-e1]-K | 0.49 ± 0.02 (3) | 115 ± 6 (3) | 0.29 ± 0.01 (2) | 0.6 ± 0.1 (3) | 0.06 ± 0.01 (3) | 0.13 ± 0.02 (3) | |
| *0.30 ± 0.01 (3) | *0.22 ± 0.01 (3) | ||||||
| K[Nt]-O | *0.11 ± 0.03 (3) | 11 ± 2 (4) | *0.06 ± 0.01 (3) | 21 ± 9 (4) | *125 ± 52 (3) | >10000 | |
| ORL1 (O) | *0.11 ± 0.01 (4) | 0.84 ± 0.02 (4) | *0.48 ± 0.05 (3) | 1.2 ± 0.1 (3) | *99 ± 12 (3) | >10000 | |
-
K i values were calculated from IC50 values determined from competition curves using [3H]diprenorphine or [3H]nociceptin (values denoted by an asterisk), according toCheng and Prussof (1973) equation. ED50 values represent concentration of unlabeled ligand that half-maximally inhibits forskolin-induced accumulation of cAMP in recombinant CHO cells expressing wild-type or hybrid receptors. Each value is mean ± S.E.M. Number of separate estimates is indicated in parentheses.