TABLE 2

Affinities of selected peptide ligands obtained using radioligand binding assays for recombinant kinin receptors The reference sequence is that of BK: H-Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9-OH.

Affinity Estimates
Peptide Human Receptors Mouse Receptors Rabbit Receptors Notes
B1 B2 B1 B2 B1 B2
nM
B2 agonists
   BK >10,000 (Ki)a 0.54 (Ki)b 200 (Ki)c 0.48 (IC50)b >5000 (Ki)d 4.5 (IC50)e
   Labradimil (RMP-7, [Hyp3, Thi5, 4-Me-Tyr8 ψ(CH2-NH)Arg9]-BK) IC50 10 nM for wild-type rat B2.f Resistant to carboxypeptidases.
Promiscuous agonist
   Kallidin (Lys-BK) 2.54 (Ki)a 0.63 (Ki)b 510 (Ki)c 0.52 (IC50)b 19 (Ki)d 2 (IC50)e
B1 agonists
   Des-Arg9-BK 1930 (Ki)a 8100 (Ki)b 0.7 (Ki)c 6400 (IC50)b 32 (Ki)d >1000 (IC50)e
   Des-Arg10-kallidin (Lys-des-Arg9-BK) 0.12 (Ki)a >30,000 (Ki)b 1.7 (Ki)c 25,000 (IC50)b 0.23 (Ki)d >1000 (IC50)e
   Sar[d-Phe8]des-Arg9-BK 60 (IC50)g 100 (IC50)h Resistant to multiple kininases.
B2 antagonists
   Icatibant (Hoe 140; d-Arg-[Hyp3, Thi5, d-Tic7, Oic8]BK) 437 (Ki)a 0.41 (IC50)b >10,000 (Ki)c 0.23 (IC50)b >5000 (IC50)d 2 (IC50)e
B1 antagonists
   [Leu8]des-Arg9-BK 276 (Ki)a >30,000 (IC50)b 4.1 (Ki)c >30,000 (IC50)b 80 (Ki)d 374 (IC50)h
   [Leu8]des-Arg10-kallidin (Lys-[Leu8]des-Arg9-BK) 0.58 (Ki)a >30,000 (IC50)b 7.5c >30,000 (IC50)b 0.43 (Ki)d >1000 (IC50)e
   B-9858 (Lys-Lys-[Hyp3, Igl5, d-Igl7, Oic8]des-Arg9-BK) 0.04 (Ki)i 146 (Ki)i 5.4 (Ki)i 44 (Ki)i 15 (IC50)h
Promiscuous antagonists
   B-9430 (d-Arg-[Hyp3, Igl5, d-Igl7, Oic8]BK) 12.6 0.25 248 (Ki)i 0.33 (Ki)i Combined blockade of B1 and B2 in vivo.j
   des-Arg10-Hoe 140 (d-Arg-[Hyp3, Thi5, d-Tic7, Oic8]-des-Arg9-BK) 174 (Ki)a 24 (Ki)c 27 (Ki)d
  • a Bastian et al., 1997

  • b Hess et al., 1994

  • c Hess et al., 1996

  • d MacNeil et al., 1995

  • e Bachvarov et al., 1995

  • f Doctrow et al., 1994

  • g G. Morissette and F. Marceau, unpublished data

  • h Sabourin et al., 2002a (binding to rabbit B1 conjugated to yellow fluorescent protein)

  • i MacNeil et al., 1997

  • j Stewart et al., 1996