2 In receptor binding studies in guinea-pig ileum preparations, Hoe 140 showed an IC50 of 1.07 x 10(-9) moll-1 and a K(I) value of 7.98 x 10(-10) moll-1.

3 In isolated organ preparations Hoe 140 and D-Arg-[Hyp2, Thi5,8, D-Phe7]BK inhibited bradykinin-induced contractions concentration dependently, with IC50-values in the guinea-pig ileum preparation of 1.1 x 10(-8) moll-1) and 3 x 10(-5) moll-1, respectively. pA2 values in this tissue were 8.42 and 6.18, respectively. In the rat uterus preparation the IC50 value was 4.9 x 10(-9) moll-1 for Hoe 140. D-Arg-[Hyp2, Thi5,8, D-Phe7]BK showed an IC50 of 4.0 x 10(-6) moll-1. The IC50 values in the guinea-pig isolated pulmonary artery were 5.4 x 10(-9) moll-1 and 6.4 x 10(-6) moll-1, respectively. In the rabbit aorta no inhibitory effects on Des-Arg9-BK induced contractions were observed.

4 In cultured bovine endothelial cells, Hoe 140 antagonized (IC50 = 10(-8) moll-1) bradykinin-induced endothelium-derived relaxing factor (EDRF) release and the bradykinin-induced increase in cytosolic free calcium (IC50 = 10(-9) moll-1).

5 Hoe 140 (10(-7) moll-1) totally suppressed the bradykinin-induced (10(-8) to 10(-4) moll-1) prostacyclin (PGI2) release from cultured endothelial cells of bovine aorta. D-Arg-[Hyp2, Thi5,8, D-Phe7]BK (10(-7) moll-1) showed a weaker antagonism.

6 Taken together these results show that Hoe 140 is a highly potent bradykinin antagonist. It was two to three orders of magnitude more potent than D-Arg-[Hyp2, Thi5,8, D-Phe7]BK.