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| EFFECT OF HOE-140, A NEW B(2) NONCOMPETITIVE ANTAGONIST, ON GUINEA-PIG TRACHEAL BRADYKININ RECEPTORS |
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| Author(s): TRIFILIEFF A, DASILVA A, LANDRY Y, GIES JP |
| Source: JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Volume: 263 Issue: 3 Pages: 1377-1383 Published: DEC 1992 |
| Times Cited: 32 References: 29 |
| Abstract: We investigated the effect of the new B2 antagonist D-Arg0[Hyp3,Thi5,D-Tic7,Oic8]bradykinin (BK) (Hoe 140) on the binding of [H-3]BK to membranes from guinea pig trachea with respect to the presence of the epithelium. Scatchard analysis of equilibrium data with [H-3]BK revealed a single class of binding sites in the epithelium denuded trachea membrane preparation (E-) with a dissociation constant (K(d)) of 55 pM and a B(max) of 0.71 fmol.mg tissue-1. When intact trachea (E+) was used, two binding sites were detected: a saturable high-affinity one (K(d) of 40 pM and B(max) of 0.69 fmol.mg tissue-1) and a low-affinity one, not really saturable, with a K(d) over 180 nM and a B(max) over 18 fmol.mg tissue-1. In guinea pig ileum, a tissue thought to contain B2 receptors, one class of binding sites was detected with a K(d) of 209.3 pM and a B(max) of 16.2 fmol.mg tissue-1. In competition experiments ([H-3]BK from 0.3 to 0.5 nM), similar results were obtained in (E+/-) and in ileum membrane preparations. B1 ligands did not displace [H-3]BK binding, demonstrating the lack of B1 receptors. BK and B2 antagonists, except Hoe 140, fully displaced [H-3]BK with Hill coefficients close to the unity. In competition studies only the high-affinity site was labeled by [H-3]BK, in the (E+) preparation, as suggested by the inhibition constant value of unlabeled BK. Hoe 140 fully displaced [H-3]BK in competition experiments, but with a Hill coefficient significantly less than unity, suggesting the presence of two binding sites for this compound in the three preparations used. In functional studies, Hoe 140 behaves as a noncompetitive antagonist of BK-induced contraction of guinea pig trachea strips without epithelium. These results indicate that the BK tracheal receptors in the guinea pig are similar to the B2 receptors present in the guinea pig ileum. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV STRASBOURG 1, NEUROIMMUNOPHARMACOL LAB, BP 24, F-67401 ILLKIRCH GRAFFENSTADEN, FRANCE |
| Publisher: WILLIAMS & WILKINS, 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 |
| Subject Category: Pharmacology & Pharmacy |
| IDS Number: KD194 |
| ISSN: 0022-3565 |
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