Functional characterization of bradykinin analogues on recombinant human bradykinin B(1) and B(2) receptors

Eur J Pharmacol. 2000 Mar 24;392(1-2):1-9. doi: 10.1016/s0014-2999(00)00046-7.


We have examined the activity of a range of kinins on recombinant human bradykinin receptors, using a high throughput functional assay which measures intracellular Ca(2+) responses. The most potent agonist for Chinese hamster ovary (CHO) cells stably expressing recombinant human bradykinin B(1) receptors were Des-Arg(9)-bradykinin (EC(50)=7.9 nM) and Des-Arg(10)-kallidin (EC(50)=8.6 nM), while the most potent agonist for CHO cells expressing human bradykinin B(2) receptors was bradykinin (EC(50)=2.0 nM). These findings confirm the validity of the recombinant system and the microtitre plate imaging-based characterization system when compared to known agonist properties of the native receptors. The concentration-response relationship for bradykinin at bradykinin B(2) receptors was potently inhibited by [D-Arg(0),Hyp(3), beta-(2-thienyl)-Ala(5),D-Tic(7),Oic(8)]-bradykinin (Hoe140) (IC(50)=71 nM), which was 500-fold more potent against the B(2)-expressing cells than the B(1) cells. Bradykinin B(1) receptor-mediated responses activated by Des-Arg(10)-kallidin were fully antagonized by Des-Arg(9)-[Leu(8)]bradykinin (IC(50)=59 nM), Des-Arg(10)-Hoe140 (IC(50)=211 nM) and most potently by Lys-Lys-Arg-Pro-Hyp-Gly-Igl-Ser-D-Igl-Oic (B9858) (IC(50)=14 nM), none of which displayed any activity against the bradykinin B(2) receptor cell line up to 3 microM. None of the antagonists displayed partial agonism activity in these cell lines. All bradykinin B(1) and B(2) receptor antagonists tested acted in an apparently non-competitive manner that is likely to be due in part to their kinetics and to the nature of the functional assay used.

MeSH terms

  • Animals
  • Bradykinin / pharmacology*
  • CHO Cells
  • Calcium / metabolism
  • Cricetinae
  • Dose-Response Relationship, Drug
  • Fluorometry
  • Humans
  • Receptor, Bradykinin B1
  • Receptor, Bradykinin B2
  • Receptors, Bradykinin / drug effects*
  • Recombinant Proteins / drug effects


  • Receptor, Bradykinin B1
  • Receptor, Bradykinin B2
  • Receptors, Bradykinin
  • Recombinant Proteins
  • Bradykinin
  • Calcium