Table 3.
Summary of ability of antagonists to block αCGRP or rAmy-stimulated cAMP accumulation in neuron-enriched rat TG cultures and Cos 7 cells transfected with rat or human CGRP receptor components
| Rat TG neurons | Rat CLR/RAMP1 | Rat CTR/RAMP1 | Human CLR/RAMP1 | Human CTR/RAMP1 | |
|---|---|---|---|---|---|
| rαCGRP | hαCGRP | ||||
| AC187 | 7.54 ± 0.36 (3)*** | <6 (4) | 8.21 ± 0.57 (3)** | <6 (4) | 8.22 ± 0.16 (4) *,++ |
| Olcegepant | 7.79 ± 0.21 (6) *** | 7.95 ± 0.12 (4) *** | <6 (4) | 9.65 ± 0.26 (5) | 7.23 ± 0.14 (4) |
| Telcagepant | 5.72 ± 0.14 (4) | 5.34 ± 0.14 (4) | 4.17 ± 0.65 (3) | 9.00 ± 0.17 (10) | 7.36 ± 0.12 (3) |
| rαCGRP8–37 | 8.12 ± 0.07 (5) *** | 8.12 ± 0.27 (3)1 | 7.20 ± 0.16 (3)1 | 7.79 ± 0.14 (6)***,+++ | 7.72 ± 0.18 (6) |
| rAmy | |||||
| AC187 | 8.07 ± 0.21 (4)+++ | <6 (4) | 8.06 ± 0.29 (4)*** | – | – |
| Olcegepant | 6.26 ± 0.06 (3) | 7.46 ± 0.16 (4) ** | <6 (3) | – | – |
| Telcagepant | – | 5.84 ± 0.30 (4) | 4.27 ± 0.31 (3) | – | – |
| rαCGRP8–37 | 7.64 ± 0.18 (4)++ | – | 7.07 ± 0.15 (4)1 | – | – |
Data are pA2 values, representing antagonist potency. Where pA2 values could not be determined they are defined as less than the highest concentration of antagonist used. Data represent mean ± SEM of n individual experiments. Comparisons were performed by Student’s t-test or one-way ANOVA followed by Tukey’s tests. TG, trigeminal ganglia; CGRP, calcitonin gene-related peptide; CLR, calcitonin receptor-like receptor; CTR, calcitonin receptor; RAMP, receptor activity-modifying protein; –, not performed.
CGRP8–37 data in transfected cells as previously reported.20 Previously reported data were not included in statistical analysis.
Comparisons shown are against telcagepant (**P < 0.01, ***P < 0.001) or olcegepant (++P < 0.01, +++P < 0.001).