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Effects of peptide and nonpeptide antagonists of bradykinin B2 receptors on the venoconstrictor action of bradykinin.
J Pharmacol Exp Ther. 1994 Jun; 269(3):1136-43.JP

Abstract

The isolated rabbit jugular and human umbilical veins respond to bradykinin (BK) by contractions that are mediated by the BK B2 type receptors. In this report, the pharmacology of recently developed BK B2 receptor antagonists is assessed by using these preparations. The nonpeptide kinin antagonist WIN 64338 (phosphonium, [[4-[[2-[[bis(cyclohexylamino)methylene]amino]- 3-(2-naphthalenyl)-1-oxopropyl]amino]phenyl]methyl]tributyl chloride monohydrochloride) demonstrates competitive and surmountable antagonism of BK in both the jugular and the umbilical veins (pA2 values of 6.14 and 5.99, respectively). WIN 64338 shows selectivity in its antagonist action as it does not inhibit the effect of various other contractile agents in either of the preparations. HOE-140 (D-Arg[hydroxyproline3,beta-thienylalanine5, D-Tic7, octahydroindol-2-yl-carbonyl residue8]-BK), a "second generation" peptide antagonist of BK, behaves as an insurmountable and irreversible antagonist in the rabbit jugular vein, but appears to be competitive in the umbilical vein (pA2 = 8.2). In the jugular vein, [L-Tic7]HOE-140 is an insurmountable antagonist about 2000-fold less potent than HOE-140; the L-Tic7 isomer demonstrates no significant antagonist activity on the umbilical vein at 30 microM. This study confirms that WIN 64338 behaves as a competitive and selective kinin antagonist of the BK B2 type receptors. The pharmacological profile of the L-Tic7 analog of HOE-140 may provide useful information in discerning the molecular interaction of noncompetitive BK antagonists with their receptors.

Authors+Show Affiliations

Centre de recherche (Université Laval), Hôtel-Dieu de Québec, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8014858

Citation

Marceau, F, et al. "Effects of Peptide and Nonpeptide Antagonists of Bradykinin B2 Receptors On the Venoconstrictor Action of Bradykinin." The Journal of Pharmacology and Experimental Therapeutics, vol. 269, no. 3, 1994, pp. 1136-43.
Marceau F, Levesque L, Drapeau G, et al. Effects of peptide and nonpeptide antagonists of bradykinin B2 receptors on the venoconstrictor action of bradykinin. J Pharmacol Exp Ther. 1994;269(3):1136-43.
Marceau, F., Levesque, L., Drapeau, G., Rioux, F., Salvino, J. M., Wolfe, H. R., Seoane, P. R., & Sawutz, D. G. (1994). Effects of peptide and nonpeptide antagonists of bradykinin B2 receptors on the venoconstrictor action of bradykinin. The Journal of Pharmacology and Experimental Therapeutics, 269(3), 1136-43.
Marceau F, et al. Effects of Peptide and Nonpeptide Antagonists of Bradykinin B2 Receptors On the Venoconstrictor Action of Bradykinin. J Pharmacol Exp Ther. 1994;269(3):1136-43. PubMed PMID: 8014858.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of peptide and nonpeptide antagonists of bradykinin B2 receptors on the venoconstrictor action of bradykinin. AU - Marceau,F, AU - Levesque,L, AU - Drapeau,G, AU - Rioux,F, AU - Salvino,J M, AU - Wolfe,H R, AU - Seoane,P R, AU - Sawutz,D G, PY - 1994/6/1/pubmed PY - 1994/6/1/medline PY - 1994/6/1/entrez SP - 1136 EP - 43 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 269 IS - 3 N2 - The isolated rabbit jugular and human umbilical veins respond to bradykinin (BK) by contractions that are mediated by the BK B2 type receptors. In this report, the pharmacology of recently developed BK B2 receptor antagonists is assessed by using these preparations. The nonpeptide kinin antagonist WIN 64338 (phosphonium, [[4-[[2-[[bis(cyclohexylamino)methylene]amino]- 3-(2-naphthalenyl)-1-oxopropyl]amino]phenyl]methyl]tributyl chloride monohydrochloride) demonstrates competitive and surmountable antagonism of BK in both the jugular and the umbilical veins (pA2 values of 6.14 and 5.99, respectively). WIN 64338 shows selectivity in its antagonist action as it does not inhibit the effect of various other contractile agents in either of the preparations. HOE-140 (D-Arg[hydroxyproline3,beta-thienylalanine5, D-Tic7, octahydroindol-2-yl-carbonyl residue8]-BK), a "second generation" peptide antagonist of BK, behaves as an insurmountable and irreversible antagonist in the rabbit jugular vein, but appears to be competitive in the umbilical vein (pA2 = 8.2). In the jugular vein, [L-Tic7]HOE-140 is an insurmountable antagonist about 2000-fold less potent than HOE-140; the L-Tic7 isomer demonstrates no significant antagonist activity on the umbilical vein at 30 microM. This study confirms that WIN 64338 behaves as a competitive and selective kinin antagonist of the BK B2 type receptors. The pharmacological profile of the L-Tic7 analog of HOE-140 may provide useful information in discerning the molecular interaction of noncompetitive BK antagonists with their receptors. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/8014858/Effects_of_peptide_and_nonpeptide_antagonists_of_bradykinin_B2_receptors_on_the_venoconstrictor_action_of_bradykinin_ DB - PRIME DP - Unbound Medicine ER -