PGE2 release by bradykinin in human airway smooth muscle cells: involvement of cyclooxygenase-2 induction

The American Journal of Physiology
L Pang, Alan J Knox

Abstract

Prostanoids may be involved in bradykinin (BK)-induced bronchoconstriction in asthma. We investigated whether cyclooxygenase (COX)-2 induction was involved in prostaglandin (PG) E2 release by BK in cultured human airway smooth muscle (ASM) cells and analyzed the BK receptor subtypes responsible. BK stimulated PGE2 release, COX activity, and COX-2 induction in a concentration- and time-dependent manner. It also time dependently enhanced arachidonic acid release. In short-term (15-min) experiments, BK stimulated PGE2 generation but did not increase COX activity or induce COX-2. In long-term (4-h) experiments, BK enhanced PGE2 release and COX activity and induced COX-2. The long-term responses were inhibited by the protein synthesis inhibitors cycloheximide and actinomycin D and the steroid dexamethasone. The effects of BK were mimicked by the B2-receptor agonist [Tyr(Me)8]BK, whereas the B1 agonist des-Arg9-BK was weakly effective at high concentrations. The B2 antagonist HOE-140 potently inhibited all the effects, but the B1 antagonist des-Arg9,(Leu8)-BK was inactive. This study is the first to demonstrate that BK can induce COX-2. Conversion of increased arachidonic acid release to PGE2 by COX-1 is mainly involved in the short-...Continue Reading

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Citations

Sep 13, 2002·American Journal of Physiology. Lung Cellular and Molecular Physiology·D A BradburyA J Knox
Apr 12, 2001·American Journal of Physiology. Heart and Circulatory Physiology·J E BrianS A Moore
Feb 21, 2003·American Journal of Respiratory Cell and Molecular Biology·Chien-Da HuangYassine Amrani
Jul 13, 2000·American Journal of Physiology. Lung Cellular and Molecular Physiology·C Y FongA J Knox
Nov 2, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·A J KnoxL Pang
May 20, 2003·American Journal of Physiology. Lung Cellular and Molecular Physiology·Linda S ChambersJanette K Burgess
Oct 7, 1998·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·L PangA J Knox
Oct 28, 1999·American Journal of Respiratory Cell and Molecular Biology·C K BillingtonR B Penn
Sep 7, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Jorge A RodriguezVictoria Velarde
Feb 4, 2003·American Journal of Physiology. Lung Cellular and Molecular Physiology·Yukihiro YagiHirokazu Tsubone
Aug 10, 2002·American Journal of Physiology. Lung Cellular and Molecular Physiology·Helen C RodgersAlan J Knox
Jun 7, 2015·American Journal of Physiology. Lung Cellular and Molecular Physiology·Karl Deacon, Alan J Knox
Feb 24, 2007·Peptides·Einat Levy, Sigal Fleisher-Berkovich

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