Table 3.

Effect of mGlu₂ mutations on NAM inhibition of LY354740-induced intracellular Ca²⁺ release

		RO4988546			RO5488608
Mutant	Position	IC50 (nM)	Ratio vs. WT	nH	IC50 (nM)	Ratio vs. WT	nH
WT		5.5 ± 0.5		−2.0 ± 0.2	11.4 ± 1.1		−2.4 ± 0.8
C616S	2.57	5.3 ± 0.7	1.0	−2.4 ± 0.6	8.9 ± 1.4	0.8	−1.8 ± 0.5
Y617F	2.58	7.2 ± 0.8	1.3	−1.5 ± 0.2	12.3 ± 4.1	1.1	−1.6 ± 0.2
T620A	2.61	4.4 ± 0.7	0.8	−1.7 ± 0.3	11.8 ± 1.8	1.0	−1.7 ± 0.3
R635A	3.28	83.5 ± 20.6	15.2	−1.7 ± 0.2	26.7 ± 6.8	2.3	−1.8 ± 0.4
R636A	3.29	22.8 ± 1.5	4.1	−1.0 ± 0.2	>1000	>100
L639A	3.32	6.6 ± 1.5	1.2	−1.5 ± 0.2	19.9 ± 4.6	1.7	−1.3 ± 0.3
A642S	3.35	5.8 ± 1.4	1.1	−1.8 ± 0.1	18.0 ± 2.6	1.6	−2.3 ± 0.2
F643A	3.36	106.4 ± 21.0	19.3	−1.3 ± 0.2	13.6 ± 3.1	1.2	−2.0 ± 0.5
S644A	3.37	4.9 ± 1.2	0.9	−1.9 ± 0.2	12.9 ± 2.9	1.1	−2.0 ± 0.1
Y647V	3.40	15.8 ± 8.2	2.9	−1.2 ± 0.3	9.5 ± 2.8	0.8	−2.2 ± 0.4
S688L-G689V	4.44–45	11.5 ± 1.9	2.1	−1.8 ± 0.2	26.7 ± 4.2	2.3	−4.5 ± 0.4
H723F	E2.52	15.9 ± 4.1	2.9	−1.4 ± 0.1	322.2 ± 175.5	28.3	−0.9 ± 0.1
H723V	E2.52	45.2 ± 8.0	8.2	−1.0 ± 0.2	93.3 ± 23.3	8.2	−1.0 ± 0.1
M728A	5.39	1.8 ± 0.4	0.3	−2.3 ± 0.5	3.5 ± 0.1	0.3	−2.5 ± 0.3
S731A	5.42	3.9 ± 0.3	0.7	−2.1 ± 0.2	10.9 ± 2.1	0.9	−2.1 ± 0.3
L732A	5.43	50.0 ± 11.8	9.1	−1.0 ± 0.1	348.9 ± 39.1	30.6	−1.0 ± 0.2
N735D	5.46	7.6 ± 1.1	1.4	−1.9 ± 0.3	14.5 ± 3.0	1.3	−1.9 ± 0.2
V736A	5.47	2.7 ± 0.4	0.5	−1.8 ± 0.3	5.3 ± 0.7	0.5	−1.8 ± 0.2
T769S	6.44	2.3 ± 0.5	0.4	−1.8 ± 0.1	10.1 ± 3.0	0.9	−2.6 ± 0.6
T769V	6.44	2.7 ± 0.6	0.5	−1.9 ± 0.03	9.5 ± 1.7	0.8	−2.0 ± 0.2
W773F	6.48	62.8 ± 11.9	11.4	−1.1 ± 0.1	21.2 ± 4.2	1.9	−1.5 ± 0.4
W773A	6.48	984.1 ± 232.9	178.9	−1.3 ± 0.6	x
L777A	6.52	4.9 ± 0.4	0.9	−1.9 ± 0.6	10.9 ± 1.8	1.0	−1.3 ± 0.1
F780A	6.55	43.7 ± 11.2	7.9	−1.2 ± 0.1	9.0 ± 2.6	0.8	−1.2 ± 0.2
T793A	7.38	5.2 ± 1.0	0.9	−1.6 ± 0.1	10.0 ± 1.4	0.9	−1.8 ± 0.2
M794A	7.39	3.9 ± 1.2	0.7	−1.6 ± 0.1	12.4 ± 2.2	1.1	−2.1 ± 0.4
C795A	7.40	3.4 ± 0.4	0.6	−1.8 ± 0.1	13.2 ± 3.4	1.2	−2.4 ± 0.7
S797A	7.42	7.0 ± 1.7	1.3	−1.5 ± 0.1	17.4 ± 3.2	1.5	−2.7 ± 0.2
V798A	7.43	8.1 ± 1.2	1.5	−1.8 ± 0.1	62.7 ± 11.4	5.5	−2.4 ± 0.3

The IC₅₀ value, ratio versus WT and Hill coefficient of RO4988546 and RO5488608 inhibition of LY354740-induced Ca²⁺ release on mGlu₂ WT and mutant receptors after transient transfection into CHO-G_α16 cells. Affected mutants are shown in bold. Data are presented as mean ± SEM and for RO4988546 the calculated values represent three to eight dose–response measurements from three to eight independent transfections and for RO5488608 the values represent three to five dose–response measurements from three to four independent transfections.