Table 3.
Agonist Pharmacology of NDP-MSH and Analogues at the Mouse Melanocortin Receptors.
| Peptide | Structure | mMC1R | mMC3R | mMC4R | mMC5R | ||||
|---|---|---|---|---|---|---|---|---|---|
| EC50 (nM) |
fold difference |
EC50 (nM) |
fold difference |
EC50 (nM) |
fold difference |
EC50 (nM) |
fold difference |
||
| NDP-MSH | Ac-Ser-Tyr-Ser-Nle-Glu-His-DPhe-Arg-Trp-Gly-Lys-Pro-Val-NH2 | 0.023±0.010 | 1 | 0.24±0.05 | 1 | 0.16±0.02 | 1 | 0.14±0.03 | 1 |
| [Ala1]NDP-MSH | Ac-Ala-Tyr-Ser-Nle-Glu-His-DPhe-Arg-Trp-Gly-Lys-Pro-Val-NH2 | 0.016±0.007 | 0.16±0.017 | 0.17±0.03 | 0.095±0.010 | ||||
| [Ala2]NDP-MSH | Ac-Ser-Ala-Ser-Nle-Glu-His-DPhe-Arg-Trp-Gly-Lys-Pro-Val-NH2 | 0.028±0.006 | 0.22±0.06 | 0.32±0.02 | 0.085±0.003 | ||||
| [Ala3]NDP-MSH | Ac-Ser-Tyr-Ala-Nle-Glu-His-DPhe-Arg-Trp-Gly-Lys-Pro-Val-NH2 | 0.024±0.0040 | 0.34±0.080 | 0.27±0.01 | 0.14±0.009 | ||||
| [Ala4]NDP-MSH | Ac-Ser-Tyr-Ser-Ala-Glu-His-DPhe-Arg-Trp-Gly-Lys-Pro-Val-NH2 | 0.11±0.020 | 5 | 0.36±0.040 | 0.39±0.10 | 0.053±0.004 | |||
| [Ala5]NDP-MSH | Ac-Ser-Tyr-Ser-Nle-Ala-His-DPhe-Arg-Trp-Gly-Lys-Pro-Val-NH2 | 0.053±0.011 | 1.18±0.40 | 5 | 0.58±0.03 | 4 | 0.25±0.012 | ||
| [Ala6]NDP-MSH | Ac-Ser-Tyr-Ser-Nle-Glu-Ala-DPhe-Arg-Trp-Gly-Lys-Pro-Val-NH2 | 0.025±0.001 | 0.55±0.12 | 0.32±0.04 | 0.29±0.16 | ||||
| [Ala7]NDP-MSH | Ac-Ser-Tyr-Ser-Nle-Glu-His- Ala-Arg-Trp-Gly-Lys-Pro-Val-NH2 | 54±21 | 2350 | 260±64 | 1080 | 380±64 | 2370 | 25±11 | 180 |
| [Ala8]NDP-MSH | Ac-Ser-Tyr-Ser-Nle-Glu-His-DPhe-Ala-Trp-Gly-Lys-Pro-Val-NH2 | 0.14±0.08 | 6 | 2.07±0.42 | 9 | 4.56±0.57 | 29 | 0.32±0.09 | |
| [Ala9]NDP-MSH | Ac-Ser-Tyr-Ser-Nle-Glu-His-DPhe-Arg-Ala-Gly-Lys-Pro-Val-NH2 | 4.05±0.72 | 180 | 295±92 | 1230 | 340±140 | 2120 | 31.0±3.34 | 220 |
| [Ala10]NDP-MSH | Ac-Ser-Tyr-Ser-Nle-Glu-His-DPhe-Arg-Trp-Ala-Lys-Pro-Val-NH2 | 0.037±0.012 | 0.13±0.06 | 0.20±0.03 | 0.11±0.02 | ||||
| [Ala11]NDP-MSH | Ac-Ser-Tyr-Ser-Nle-Glu-His-DPhe-Arg-Trp-Gly-Ala-Pro-Val-NH2 | 0.010±0.003 | 0.17±0.02 | 0.23±0.03 | 0.094±0.005 | ||||
| [Ala12]NDP-MSH | Ac-Ser-Tyr-Ser-Nle-Glu-His-DPhe-Arg-Trp-Gly-Lys-Ala-Val-NH2 | 0.096±0.034 | 4 | 0.36±0.06 | 0.83±0.18 | 5 | 0.18±0.03 | ||
| [Ala13]NDP-MSH | Ac-Ser-Tyr-Ser-Nle-Glu-His-DPhe-Arg-Trp-Gly-Lys-Pro-Ala-NH2 | 0.058±0.021 | 0.30±0.06 | 0.35±0.09 | 0.24±0.04 | ||||
The indicated errors represent the standard error of the mean determined from at least three independent experiments. All compounds were full agonists.