Compound | Peak Ins(1,4,5)P3 response | Binding affinity constants | Maximal internalization of receptors | Maximal increase in endocytotic rate constant | ||||
---|---|---|---|---|---|---|---|---|
Rmax1-a | EC50 | Ki | Hill slope | Imax | EC50 | ke (max) | EC50 | |
% | μm | μm | % | μm | min−1 | μm | ||
Carbachol | 100 | 73.9 ± 1.91-b | 155 ± 20 | 0.88 ± 0.02 | 90.4 ± 0.7 | 3.5 ± 0.21-b | 0.545 ± 0.045 | 23.7 ± 2.01-b |
Oxotremorine-M | 96.7 ± 2.5 | 6.57 ± 2.951-b | 23.2 ± 3.3 | 0.74 ± 0.01 | 90.3 ± 1.7 | 0.75 ± 0.121-b | 0.553 ± 0.092 | 6.68 ± 2.091-b |
Methacholine | 94.0 ± 11.8 | 38.7 ± 7.0 | 57.9 ± 20.1 | 0.84 ± 0.07 | 89.1 ± 1.1 | 4.8 ± 1.31-b | 0.486 ± 0.059 | 40.3 ± 15.5 |
Bethanechol | 51.6 ± 11.0 | 1197 ± 2381-c | 407 ± 32 | 0.97 ± 0.08 | 82.0 ± 0.6 | 128 ± 191-b | 0.261 ± 0.011 | 552 ± 87 |
Arecoline | 26.1 ± 3.9 | 147 ± 351-c | 15.5 ± 0.9 | 0.90 ± 0.04 | 78.4 ± 2.3 | 6.9 ± 2.41-b | 0.184 ± 0.012 | 38.1 ± 22.3 |
Pilocarpine | 8.4 ± 1.2 | 127 ± 63 | 14.6 ± 1.4 | 0.99 ± 0.04 | 18.7 ± 0.7 | 57.2 ± 10.11-c | 0.013 ± 0.001 | 68.5 ± 11.41-c |
McN-A-343 | No effect | 35.6 ± 9.0 | 0.96 ± 0.14 | No effect | No effect | |||
N-Methylatropine | No effect | 0.00172 ± 0.00089 | 0.91 ± 0.10 | No effect | No effect |
The ability of the muscarinic ligands to stimulate Ins(1,4,5) P3 production and internalization of receptors was measured as described in the text. Transformation of internalization data to yield increases in the endocytotic rate constant k e was performed using eq. 4.