Premium
Agonistic and antagonistic properties of the bradykinin B 2 receptor antagonist, Hoe 140, in isolated blood vessels from different species
Author(s) -
Félétou Michel,
Germain Martine,
Thurieau Christophe,
Fauchère JeanLuc,
Canet Emmanuel
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb13130.x
Subject(s) - bradykinin , schild regression , medicine , endocrinology , antagonist , agonist , bradykinin receptor , competitive antagonist , chemistry , contraction (grammar) , receptor , pharmacology , biology
1 Hoe 140, a recently described bradykinin B 2 antagonist, and NPC 567 from an earlier generation of bradykinin B 2 antagonists, were tested in rabbit and sheep isolated blood vessels. 2 In rabbit jugular vein, a bradykinin B 2 preparation, NPC 567 was an antagonist (apparent pA 2 : 8.67 ± 0.16) with marked residual agonistic activity (log[EC 50 ]: −7.29 ± 0.13). Hoe 140 was a potent non‐competitive antagonist devoid of agonistic properties (slope of the Schild plot: 2.02; estimated pA 2 : 9.04). 3 In rabbit aorta, a bradykinin B 1 preparation, NPC 567 was a competitive antagonist (pA 2 : 6.32 ± 0.13) but Hoe 140 was ineffective. The two antagonists did not show any agonistic properties in this tissue. 4 In sheep femoral artery without endothelium, bradykinin and Hoe 140 induced contractions with identical efficacy and similar potency (log[EC 50 ]: −8.05 ± 0.12, −7.73 ± 0.10; maximal contraction in % of KCl [60 m m ]: 59.5 ± 15.1, 62.0 ± 13.1; for bradykinin and Hoe 140, respectively). In contrast NPC 567 was an extremely weak agonist. The contractile responses to bradykinin and Hoe 140 were inhibited by NPC 567 (apparent p K B : 6.89 ± 0.22 and 6.58 ± 0.08 versus bradykinin and Hoe 140, respectively) but not by a B 1 bradykinin antagonist, suggesting that the receptor involved was a bradykinin B 2 receptor. 5 In sheep femoral artery with endothelium, bradykinin induced a biphasic response: an endothelium‐dependent relaxation and a contraction which were both inhibited by NPC 567 (apparent p K B : 7.10 ± 0.15) and Hoe 140 (pA 2 : 8.38 ± 0.12). As bradykinin B 2 receptor antagonists, Hoe 140 and NPC 567 were less potent in the sheep femoral artery than in the rabbit jugular vein. Neither Hoe 140 nor NPC 567 were agonists for the endothelial receptor. 6 This study demonstrates that Hoe 140, a new bradykinin B 2 receptor antagonist, is more selective and more potent than NPC 567; however, it may possess, depending on the tissue studied, marked residual agonistic properties. Furthermore, bradykinin B 2 receptors are subject to important species specificity. Finally, two different bradykinin B 2 receptor subtypes may coexist in the sheep femoral artery with endothelium.