Fig. 5: Bioactivities of selected bradykinin azapeptide analogues.
a Selected bradykinin azapeptide analogues displace a radioactive B2R receptor ligand in the nanomolar range (IC50’s) and induce fibroblast prostaglandin E2 (PGE2) production (EC50) in vitro. EC50’s for bradykinin- and bradykinin azapeptide analogue-induced PGE2 release (right most column) were determined by least squares regression analysis of data plotted in Fig. 5b without weighting and were not significantly different between data sets, as determined by one-way ANOVA on ranks (Kruskal–Wallis H-test). b Bradykinin and bradykinin azapeptide analogues azaP2-BK (63), azaF8-BK (68) and [azaP2, azaF8]-BK (70) dose-dependently stimulate the production of PGE2 in 3T3 cells. Subconfluent monolayers of 3T3 cells were incubated with test compounds for 7 min in serum-free medium and supernatants were collected and analyzed for PGE2 by ELISA. Values are means ± SEM of raw PGE2 ELISA data from three independent dose-response experiments performed with triplicates (see Supplementary Fig. 6 for an alternative bar plot showing individual data points from each of the three independent experiments used to calculate the mean ± SEM of PGE2 release data plotted in Fig. 5b as well as the amount of PGE2 released by control-treated cells). c B2R antagonist Icatibant blocks lowering effects of bradykinin azapeptide (azaF8-BK (68) on mean arterial pressure (MAP) in rats). Icatibant (10 µg/kg) was injected as IV-bolus 15 min before azaF8-BK administration. The solid horizontal lines represent mean values from individual rats (n = 2). Asterisks denote p < 0.05 one-tailed (p-values from left to right: no pre-treatment 0.0362, 0.0014; pre-treatment 0.0003).
