Table 1. Receptor binding affinity and pharmacological activity of kinin derivatives at human B1R and B2R.
| Peptide sequence | HEK-293T (receptor binding) |
hUV (bioassay) |
||
|---|---|---|---|---|
| hB1R | hB2R | hB1R | hB2R | |
| IC50 (nM) | IC50 (nM) | EC50 (nM) | EC50 (nM) | |
| Natural agonist | ||||
| BK | >10 000a | 4.9a | >10 000a | 3.0a |
| LysdesArg9BK | 6.3b | >10 000b | 3.9b | >10 000a |
| Synthetic agonist | ||||
| [Hyp3,Thi5,NChg7,Thi8]-BK (NG291) | >10 000a | 1.8a | n.d. | 1.8a |
| SarLys[dPhe8]-desArg9BK (NG29) | 0.3b | > 10 000b | 0.45b | n.d. |
| B1R/B2R dimeric agonist | 28 | 40 | 32 | 50 |
Data taken from aBélanger et al.11. bCoté et al.13 Competition binding assays were performed with [3H]-BK (B2R agonist) (1 nM) and [3H]-LysDesArg9-BK (B1R agonist) (1 nM) using adherent HEK-293T cells transiently transfected with human B1R or B2R. Binding affinity of the peptides is expressed in terms of IC50 value. For functional experiments, complete concentration-contractile response curves to agonists were performed on human de-endothelized umbilical veins (hUV) according to Gobeil et al.14 Agonist potencies of the heterodimer at the B1R and the B2R were determined following B2R blockade with HOE140 and B1R blockage with R954 (applied at 5 μM), respectively. EC50 values derived from these curves are shown. n.d., not determined.