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Molecular Pharmacology

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Abstract

Evidence for a pulmonary B3 bradykinin receptor.

S G Farmer, R M Burch, S A Meeker and D E Wilkins
Molecular Pharmacology July 1989, 36 (1) 1-8;
S G Farmer
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R M Burch
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S A Meeker
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D E Wilkins
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Abstract

We have examined pulmonary effects of bradykinin (Bk) in vivo and in vitro in guinea pigs and their potential inhibition by antagonists of Bk B1 and B2 receptors. Bk was a potent bronchoconstrictor in vivo and caused contractions of isolated, epithelium-denuded trachealis. D-Arg[Hyp3,D-Phe7]-Bk (NPC567) and D-arg[Hyp3,Thi5,8,D-Phe7]-Bk (NPC349), B2 receptor antagonists, were weak inhibitors of Bk-induced bronchoconstriction in vivo and were virtually inactive as antagonists of Bk-induced airway smooth muscle contraction. Several other B2 antagonists as well as B1 antagonist, des-Arg9-[Leu8]-Bk, did not inhibit Bk-induced tracheal contraction. The B1 receptor agonist des-Arg9-Bk was without effect on tracheal tone. Tracheal responses to Bk were unaffected by antagonists of muscarinic, histamine, serotonin, and catecholamine receptors. The inability of the antagonists to inhibit Bk is unlikely to be due to their degradation, because NPC567 was only weakly active in the presence of inhibitors of kininase I (EC 3.4.11.2), kininase II (EC 3.4.15.1), and neutral endopeptidase (EC 3.4.24.11). These studies were corroborated by ligand binding experiments in guinea pig and ovine airways. In [3H]Bk binding, the Bk antagonists had no effect in guinea pig trachea, slightly displaced [3H]Bk in ovine trachea, and inhibited approximately 60% of total specific binding in lung. des-Arg9-[Leu8]-Bk and several other agents, including atropine, neurokinin A, substance P, and vasoactive intestinal peptide, had no effect on lung Bk binding. Bk and its analogs were not degraded during the binding assay. These data suggest that pulmonary tissue, particularly in the large airways, contains a novel Bk binding site, a B3 receptor, which may be involved in Bk-induced bronchoconstriction.

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Molecular Pharmacology
Vol. 36, Issue 1
1 Jul 1989
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Abstract

Evidence for a pulmonary B3 bradykinin receptor.

S G Farmer, R M Burch, S A Meeker and D E Wilkins
Molecular Pharmacology July 1, 1989, 36 (1) 1-8;

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Abstract

Evidence for a pulmonary B3 bradykinin receptor.

S G Farmer, R M Burch, S A Meeker and D E Wilkins
Molecular Pharmacology July 1, 1989, 36 (1) 1-8;
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