TABLE 2.

Effect of the substitutions of the conserved amino acid residues of hMC4R on NDP-MSH binding and cAMP production

	Receptor expression	NDP-MSH Ki	NDP-MSH EC5O
	%WT	nM
hMC4R-WT	100	3.6 ± 0.1	0.8 ± 0.2
D90A	47 ± 6.3	7.4 ± 0.1	NRa
M91A	97 ± 3.3	4.8 ± 0.1	1.8 ± 0.7
S94A	97 ± 6.3	4.5 ± 0.1	1.4 ± 0.5
E100A	82 ± 11	12.0 ± 2.9b	5.7 ± 0.5b
D122A	78 ± 11	10.9 ± 1.6b	9.8 ± 3.2b
D126N	35 ± 10	NDc	353 ± 43.2b
S127A	91 ± 8.3	4.3 ± 0.5	1.6 ± 0.8
S131A	94 ± 4.3	4.7 ± 0.9	1.7 ± 0.6
T178A	94 ± 3.6	3.1 ± 0.2	1.0 ± 0.1
F201A	95 ± 5.8	4.3 ± 0.5	1.2 ± 0.2
M204A	98 ± 5.8	3.0 ± 0.9	1.1 ± 0.1
F254A	91 ± 6.3	4.0 ± 0.9	9.2 ± 0.1
W258A	89 ± 3.9	14.0 ± 1.9b	9.2 ± 0.3b
F261A	81 ± 8.3	28 ± 2.9b	19 ± 1.8b
H264A	78 ± 4.5	>103b	141 ± 13.1b

^aNR, no response.

^bp < 0.05 compared with WT receptor.

^cND, no binding.