JPET xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tsukagoshi, H.
Right arrow Articles by Chung, K. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tsukagoshi, H.
Right arrow Articles by Chung, K. F.

Bradykinin receptor subtypes in rat lung: effect of interleukin-1 beta

H Tsukagoshi, EB Haddad, PJ Barnes and KF Chung

Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.

We have characterized bradykinin (BK) receptors in the rat lung and studied the effect of recombinant human interleukin-1 beta (IL-1 beta) on BK receptors in vitro and in vivo. In lung membranes, saturation studies with [3]BK revealed a single class of specific and saturable binding sites. The BK B1 antagonist des-Arg9[Leu8]-BK was less effective in displacing [3H]BK binding sites from lung membranes. In contrast, the selective BK B2 antagonists, Hoe 140 (D-Arg-[Hyp3,Thi5,D- Tic7,Oic8]-BK) and NPC 567 (D-Arg-[Hyp3,D-Phe7]-BK) fully inhibited the binding of [3H]BK to lung membranes with Ki values of 96.7 +/- 17.8 pM and 9.0 +/- 2.5 nM, respectively. Intratracheal administration of 500 U of IL-1 beta induced airway hyper-responsiveness to inhaled BK and neutrophilia in bronchoalveolar lavage fluid 18 to 24 hr later. Compared to naive or saline-treated animals, IL-1 beta had no effect on [3H]BK binding characteristics at 4, 12 or 24 hr after IL-1 beta administration. Twenty-four hours after IL-1 beta instillation, there was no change in the affinity of the selective BK B1 or B2 antagonists when compared to control animals. In vivo, the selective BK B2 receptor antagonists, NPC 567 (3 mumol kg-1 i.v.) and Hoe 140 (100 nmol kg-1 i.v.), inhibited BK-induced increase in lung resistance, whereas the selective BK B1 antagonist, des-Arg9[Leu8]-BK (10 mumol kg-1 i.v.), was without effect. These data suggest that the action of BK in the rat lung is dependent mainly on the activation of the BK B2 receptor subtype.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 273, Issue 3, pp. 1257-1263, 06/01/1995
Copyright © 1995 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 Pharmacol. Rev.Home page
P. J. Barnes
Mediators of Chronic Obstructive Pulmonary Disease
Pharmacol. Rev., December 1, 2004; 56(4): 515 - 548.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
T.-J. HUANG, E.-B. HADDAD, A. J. FOX, M. SALMON, C. JONES, G. BURGESS, and K. F. CHUNG
Contribution of Bradykinin B1 and B2 Receptors in Allergen-induced Bronchial Hyperresponsiveness
Am. J. Respir. Crit. Care Med., November 1, 1999; 160(5): 1717 - 1723.
[Abstract] [Full Text]

Home page
 Mol. Pharmacol.Home page
F. Schmidlin, D. Scherrer, L. Daeffler, C. Bertrand, Y. Landry, and J.-P. Gies
Interleukin-1beta Induces Bradykinin B2 Receptor Gene Expression through a Prostanoid Cyclic AMP-Dependent Pathway in Human Bronchial Smooth Muscle Cells
Mol. Pharmacol., June 1, 1998; 53(6): 1009 - 1015.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1995 by the American Society for Pharmacology and Experimental Therapeutics.