TABLE 2

Mutations in o2 region

Affinities (expressed as p Kapp) for gallamine and W84 are shown, along with half-times of dissociation of [3H]NMS in the absence of allosteric modulators. To facilitate comparisons, the affinit y data have also been transformed to a scale of relative difference between the p Kapp values of the human M2 and M5 receptors (see Materials and Methods). Data shown represent mean ± S.E.M. from three or more assays for p Kapp values and six or more assays for half-times. Receptors were expressed in COS-7 cell membranes.

Receptors t½ pKapp Values Relative pKapp
Gallamine W84 Gallamine W84
min mean ± S.E.M. %
M2 4.3 ± 0.4 6.99 ± 0.06 7.66 ± 0.10 100 100
M5 95.2 ± 0.6 5.02 ± 0.04 5.66 ± 0.07 0 0
M2 E172L 4.2 ± 0.2 6.79 ± 0.09 7.53 ± 0.10 89.8 93.5
M2 E172P 3.5 ± 0.2 6.64 ± 0.04 7.32 ± 0.09 82.2 83.0
M2 E175Q 4.4 ± 0.1 6.65 ± 0.09 7.43 ± 0.11 82.7 88.5
M2 Y177Q 4.2 ± 0.4 6.70 ± 0.07 5.99 ± 0.08 85.3 16.5
M2 E172L, E175Q 5.7 ± 0.5 6.36 ± 0.10 6.89 ± 0.09 68.0 61.5
M2 EDGE-LAGQ 5.0 ± 0.2 6.17 ± 0.07 7.14 ± 0.08 58.4 74.0
M5 P179E 52.2 ± 1.8 5.49 ± 0.02 5.57 ± 0.12 23.9 −4.5
M5 Q184Y 127.5 ± 5.7 5.16 ± 0.11 6.22 ± 0.11 7.1 28.0
M5 P179E, Q184Y 95.7 ± 3.9 5.69 ± 0.04 6.86 ± 0.08 34.0 60.0
CR3 81.5 ± 4.0 5.26 ± 0.08 6.97 ± 0.12 12.2 69.5
CR3 Y177Q 88.0 ± 3.0 5.23 ± 0.03 5.36 ± 0.08 10.7 −15.0