TABLE 1.
Antagonist activities of lipidated αCGRP8-37 analogues at calcitonin-family receptors expressed in Cos-7 cells or SK-N-MC cells with endogenous CGRP receptor expression.
| αCGRP8-37 | αCGRP7-37-palmitate | V8C-palmitate | K24C-palmitate | K35C-palmitate | |
|---|---|---|---|---|---|
| CGRPr (pKB) | 9.09 ± 0.16 (5) | 8.78 ± 0.06 (4) | 9.35 ± 0.17 (5) | 8.58 ± 0.25 (5) | 7.24 ± 0.20 (5) a |
| AMY1r (pKB) | 7.12 ± 0.13 (5) | 8.80 ± 0.18 (5) a | 8.26 ± 0.21 (5) a | 8.75 ± 0.10 (5) a | 6.01 ± 0.12 (5) a |
| AM1r (pA2) | 7.36 ± 0.11 (9) | 8.53 ± 0.17 (5) a | 8.73 ± 0.17 (5) a | 9.23 ± 0.16 (5) a | 6.30 ± 0.14 (5) a |
| AM2r (pA2) | 7.32 ± 0.20 (9) | 8.55 ± 0.16 (5) a | 8.18 ± 0.13 (5) b | 9.18 ± 0.18 (5) a | 6.60 ± 0.21 (5) b |
| CTr (pA2) | — c | 7.11 ± 0.10 (5) | 6.85 ± 0.13 (5) | 6.21 ± 0.19 (5) | 5.39 ± 0.30 (3) d |
| SK-N-MC (pA2) | 9.58 ± 0.15 (6) | 10.50 ± 0.19 (5) e | 10.45 ± 0.24 (5) e | 10.14 ± 0.17 (5) | 7.78 ± 0.25 (5) a |
Values are mean ± SEM of (n) independent experiments. pKB or pA2 comparisons to αCGRP8-37 were analyzed by one-way ANOVA followed by Dunnett’s multiple comparison test.
a
p < 0.001.
b
p < 0.05
c
αCGRP8-37 was too weak to generate a pA2 in the pilot experiments and sCT8-32 was used as a positive control for the CT receptor.
d
Denotes that five experiments were conducted but only (n) repeats elicited measurable pA2 values.
e
p < 0.01