Table 1.
MC4R Genotype | Bmax (%C)a | NDP-MSH Binding | NDP-MSH-stimulated cAMP | α-MSH Binding | α-MSH-stimulated cAMP | ||
---|---|---|---|---|---|---|---|
|
|
||||||
IC50 (nM) | EC50 (nM) | Rmax (%C)b | IC50 (nM) | EC50 (nM) | Rmax (%C)c | ||
|
|
|
|||||
Common | 100 | 33.93 ± 4.19 | 1.60 ± 0.27 | 100 | 606.28 ± 139.34 | 10.81 ± 5.04 | 100 |
G55V | 55.40 ± 9.63e | 47.63 ± 16.26 | 5.41 ± 1.17d | 97.08 ± 6.46 | N/D | 612.34 ± 210.05d | 84.87 ± 4.82d |
R165G | 37.18 ± 3.07f | 3.24 ± 0.40e | 1.34 ± 0.22 | 135.46 ± 13.02 | 271.20 ± 65.53 | 5.18 ± 1.32 | 112.50 ± 4.51 |
R165Q | 34.75 ± 4.44f | 2.78 ± 0.35e | 0.91 ± 0.08d | 142.68 ± 6.64d | 365.83 ± 86.87 | 4.46 ± 0.50 | 134.40 ± 5.28d |
C172R | N/D | N/D | 9.60 ± 2.22d | 32.86 ± 6.69e | N/D | 1627.96 ± 430.15e | 39.21 ± 7.91e |
F202L | 99.24 ± 9.32 | 26.74 ± 5.92 | 2.15 ± 0.50 | 125.99 ± 8.55 | 492.63 ± 83.57 | 2.79 ± 0.58 | 92.67 ± 12.58 |
M208V | 74.16 ± 6.18e | 70.38 ± 15.20 | 17.77 ± 5.14d | 113.88 ± 13.65 | 913.47 ± 224.19 | 270.75 ± 122.34d | 139.40 ± 22.24 |
I269N | 42.86 ± 3.08f | 10.73 ± 1.39d | 0.63 ± 0.23 | 131.12 ± 9.65 | 561.20 ± 42.92 | 40.42 ± 23.73 | 121.30 ± 6.83d |
A303P | 22.42 ± 4.55f | 2.29 ± 0.34e | 0.57 ± 0.13e | 98.49 ± 9.23 | 54.98 ± 14.23d | 1.00 ± 0.06 | 108.30 ± 2.97 |
Abbreviations: MC4R, melanocortin-4 receptor; NDP-MSH, 4-Norleucine, 7-D-phenylalanine-alpha-melanocyte-stimulating hormone (ultra-potent MC4R agonist); α-MSH, alpha-melanocyte-stimulating hormone; Bmax, maximal binding of 125I-NDP-MSH to cells transiently transfected with common or variant MC4R; %C, percentage of value for common sequence of MC4R; IC50, half-maximal inhibitory concentration; EC50, half-maximal effective concentration; cAMP, 3′-5′-cyclic adenosine monophosphate; Rmax, maximal response; N/D, could not be detected or calculated; SEM, standard error of the mean.
Bmax are mean ± SEM of at least six independent experiments, and other parameters are mean ± SEM of at least three independent experiments. Independent samples t tests compared variant MC4Rs with common MC4R.
Rmax of common MC4R was 3544.33 ± 471.12 pmol/106 cells with NDP-MSH stimulation.
Rmax of common MC4R was 3117.01 ± 472.62 pmol/106 cells with α-MSH stimulation.
Significantly different from common MC4R, P <0.05.
Significantly different from common MC4R, P <0.01.
Significantly different from common MC4R, P <0.001.