Antagonism of agonist-mediated M1 mAChR activation of nNOS
| Agonist | Antagonist | pKB1-a | s1-b | df1-c |
|---|---|---|---|---|
| CCh | Atropine | 8.69 ± 0.14 | 0.99 ± 0.25 | 32 |
| Xanomeline | 8.32 ± 0.16 | 0.84 ± 0.28 | 22 | |
| CCh | Pirenzepine | 7.74 ± 0.08 | 1.10 ± 0.11 | 13 |
| Xanomeline | 7.92 ± 0.671-d | 1.10 ± 0.62 | 13 |
Enzyme activity was assayed by measuring the conversion ofl-[3H]arginine tol-[3H]citrulline in response to agonist for 1 h at 37°C in a HEPES-based buffer, as described in the text and shown in Figs. 4 and 6. Parameters (±S.E.M.) were derived from computer-assisted nonlinear regression analysis, according to eq. 2 in the text.
↵1-a Negative logarithm of the antagonist dissociation equilibrium constant, estimated with the slope parameter constrained to unity.
↵1-b Equivalent to the Schild slope parameter. None of these values were significantly different (p > .05) from 1.
↵1-c Degrees of freedom.
↵1-d pA2 value only; agonist concentration-response curves did not conform to simple competition in the presence of the antagonist.