TABLE 2

Pharmacological parameters of affinity (pKi or pKB) and potency (pEC50) of orthosteric ligands at the WT and N410K+T423K M2 mAChRs

Values represent the mean ± S.E. from at least three experiments performed in duplicate.

ParametersWTN410K+T423Kna
[3H]NMS binding
pKib
  ACh6.06 ± 0.057.71 ± 0.07*5
  Atropine8.71 ± 0.048.96 ± 0.075
[35S]GTPγS
pEC50c
  ACh6.28 ± 0.066.70 ± 0.07*3
pKBd
  Atropine8.88 ± 0.099.00 ± 0.093
pERK1/2
 pEC50c
  ACh7.99 ± 0.098.76 ± 0.09*3
pKBd
  Atropine9.10 ± 0.179.38 ± 0.173
  • pERK1/2, phosphorylated ERK1/2.

  • a Number of experiments performed.

  • b Negative logarithm of the orthosteric ligand equilibrium dissociation constant.

  • c Negative logarithm of agonist potency.

  • d Negative logarithm of the orthosteric antagonist equilibrium dissociation constant derived from functional interactions with ACh.

  • * Significantly different from the corresponding value at the wild type (P < 0.05), Student’s t test.