Table 2. Tetrapeptide Agonist (EC50) and Antagonist (pA2) Receptor Pharmacologically at the mMC3R and mMC4R (Mean ± SEM)a.
| mMC3R |
mMC4R |
||||
|---|---|---|---|---|---|
| analogue | structure | EC50 (nM) | pA2 | EC50 (nM) | pA2 |
| MTII | Ac-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-NH2 | 0.35 ± 0.02 | none | 0.05 ± 0.01 | none |
| SHU9119 | Ac-Nle-c[Asp-His-DNal(2′)-Arg-Trp-Lys]-NH2 | 54% at 1 μM | 8.7 ± 0.3 | >100,000 | 9.7 ± 0.2 |
| 3.0 ± 0.7 | |||||
| NDP-MSH (6–9) | Ac-His-DPhe-Arg-Trp-NH2 | 64 ± 19 | none | 5.4 ± 2.0 | none |
| 1 | Ac-Trp-(pI)DPhe-Arg-Trp-NH2 | >100,000 | 5.4 ± 0.2 | >100,000 | 7.8 ± 0.1 |
| 2 | Ac-Trp-(pI)DPhe-Arg-Bip-NH2 | >100,000 | none | >100,000 | 6.3 ± 0.1 |
| 3 | Ac-Trp-(pI)DPhe-Arg-3Bal-NH2 | >100,000 | none | >100,000 | 7.1 ± 0.1 |
| 4 | Ac-Trp-(pI)DPhe-Arg-Tic-NH2 | 48% at 100 μM | none | 44% at 100 μM | 6.0 ± 0.2 |
| 5 | Ac-Trp-(pI)DPhe-Arg-Phe-NH2 | 66% at 100 μM | >100,000 | 44% at 100 μM | 6.8 ± 0.2 |
| 6 | Ac-Trp-(pI)DPhe-Arg-Nal(2′)-NH2 | >100,000 | 5.9 ± 0.2 | >100,000 | 8.3 ± 0.1 |
| 7 | Ac-Trp-(pI)DPhe-Arg-DNal(2′)-NH2 | >100,000 | 5.7 ± 0.1 | >100,000 | 8.3 ± 0.1 |
a
The reported errors are the standard error of the mean of at least three independent experiments. The pA2 values were calculated by a Schild analysis and used MTII as the agonist compound. A value of >100,000 nM indicates that no agonist activity was observed at the concentrations tested. A % at 100 μM indicates some agonist activity was observed with the corresponding percentage indicating the amount of activity relative to the MTII-induced maximal response.