Table 3.
Potency (pEC50), affinity (pKA) and coupling efficacy (log τ) values for various GLP-1 receptor agonists from yeast assays
| Ligand | GPA1/Gαs | GPA1/Gαi | GPA1/Gαs | GPA1/Gαi | ||||
|---|---|---|---|---|---|---|---|---|
| pEC50a | Emaxb | pEC50a | Emaxb | pKAc | log τd | pKAc | log τd | |
| GLP-1 | 8.1 ± 0.10*** | 100 ± 5.4*** | 7.5 ± 0.1 | 75.7 ± 5.6 | 6.7 ± 0.2** | 1.0 ± 0.2** | 6.7 ± 0.3 | 0.7 ± 0.2 |
| Glucagon | 6.5 ± 0.40*** | 48.7 ± 6.6*** | 6.9 ± 0.5 | 82.6 ± 8.0 | 6.2 ± 0.2** | −0.1 ± 0.3** | 6.4 ± 0.3 | 0.4 ± 0.2 |
| Oxyntomodulin | 6.7 ± 0.20*** | 103 ± 7.2*** | 7.7 ± 0.3 | 76.6 ± 7.0 | 5.4 ± 0.2** | 1.3 ± 0.01** | 6.8 ± 0.4 | 0.3 ± 0.1 |
| Exenatide | 6.5 ± 0.07*** | 53.6 ± 8.0*** | 6.6 ± 0.2* | 87.7 ± 5.4 | 6.3 ± 0.4** | −0.02 ± 0.3** | 6.2 ± 0.6 | 0.5 ± 0.4 |
| Liraglutide | 7.5 ± 0.06*** | 99.1 ± 7.9*** | 7.1 ± 0.06 | 84.6 ± 5.3 | 6.4 ± 0.4** | 0.9 ± 0.3** | 6.5 ± 0.7 | 0.5 ± 0.5 |
All values are mean ± SEM of five independent experimental repeats. Statistical significance compared with GLP-1 (*P < 0.05; **P < 0.01; ***P < 0.001) was determined by one-way anova with Dunnett's post-test.
The negative logarithm of the agonist concentration required to produce a half-maximal response.
The maximal response to the ligand expressed as a percentage of that obtained in the absence of antagonist.
The negative logarithm of the equilibrium disassociation constant for each ligand generated through use of the operational model of agonism (Black and Leff, 1983).
τ is the coupling efficiency parameter, generated by comparison to the natural ligand, GLP-1 using the operational model of agonism.