FR 172357, a new non-peptide antagonist of the kinin B(2) receptor was tested in three isolated vessels, the human umbilical vein, the rabbit jugular vein, and the pig coronary artery, to evaluate its antagonistic activities against bradykinin. FR 172357 displaced to the right the concentration-response curves of bradykinin. The displacements were parallel to the controls without reduction of the maximum effect in the human umbilical vein and in the rabbit jugular vein, but not in the pig coronary artery. Schild plots confirmed that FR 172357 acts as a competitive antagonist in the human umbilical vein (pA(2) 8.65) and in the rabbit jugular vein (pA(2) 9. 07), and as a non-competitive antagonist in the pig coronary artery (pK(B) 10.14). FR 172357 is selective for the kinin B(2) receptor since it does not influence the effects of Lys-des-Arg(9)-bradykinin in the human umbilical vein, in the rabbit aorta, and in the pig renal vein. It is specific because it does not affect the contractions induced by angiotensin II, noradrenaline, 5-hydroxytryptamine, or endothelin-1 in the human umbilical vein. It, however, interacts with the tachykinin NK(1) receptor of the rabbit jugular vein and pig coronary artery. Compared to other bradykinin B(2) receptor antagonists, FR 172357 emerges as a very potent compound, which may represent a choice for experimental (and clinical?) applications.

Characterization of FR 172357, a new non-peptide bradykinin B2 receptor antagonist, in human, pig and rabbit preparations

RIZZI, Anna;CALO', Girolamo;JORIZZO, Gianfranco;AGNELLO, Giovanni;MOLLICA, Gioacchino;REGOLI, Domenico
1999

Abstract

FR 172357, a new non-peptide antagonist of the kinin B(2) receptor was tested in three isolated vessels, the human umbilical vein, the rabbit jugular vein, and the pig coronary artery, to evaluate its antagonistic activities against bradykinin. FR 172357 displaced to the right the concentration-response curves of bradykinin. The displacements were parallel to the controls without reduction of the maximum effect in the human umbilical vein and in the rabbit jugular vein, but not in the pig coronary artery. Schild plots confirmed that FR 172357 acts as a competitive antagonist in the human umbilical vein (pA(2) 8.65) and in the rabbit jugular vein (pA(2) 9. 07), and as a non-competitive antagonist in the pig coronary artery (pK(B) 10.14). FR 172357 is selective for the kinin B(2) receptor since it does not influence the effects of Lys-des-Arg(9)-bradykinin in the human umbilical vein, in the rabbit aorta, and in the pig renal vein. It is specific because it does not affect the contractions induced by angiotensin II, noradrenaline, 5-hydroxytryptamine, or endothelin-1 in the human umbilical vein. It, however, interacts with the tachykinin NK(1) receptor of the rabbit jugular vein and pig coronary artery. Compared to other bradykinin B(2) receptor antagonists, FR 172357 emerges as a very potent compound, which may represent a choice for experimental (and clinical?) applications.
Rizzi, C; Rizzi, Anna; Calo', Girolamo; Jorizzo, Gianfranco; Agnello, Giovanni; Mollica, Gioacchino; Inamura, N; Regoli, Domenico
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1198677
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