Bradykinin augments EGF-induced airway smooth muscle proliferation by activation of conventional protein kinase C isoenzymes

European Journal of Pharmacology
Reinoud GosensS Adriaan Nelemans

Abstract

This study aims to investigate the effects of bradykinin, alone and in combination with growth factors on proliferation of cultured bovine tracheal smooth muscle cells. Bradykinin did not induce mitogenic responses by itself, but concentration-dependently augmented growth factor-induced [3H]thymidine incorporation and cell proliferation. The bradykinin effect was mediated by bradykinin B2 receptors, and not dependent on cyclo-oxygenase. Bradykinin-induced synergism with epidermal growth factor (EGF) could be suppressed by the protein kinase C (PKC) inhibitors GF 109203X (Bisindolylmaleimide I; specific for conventional and novel PKCs) and Gö 6976 (12-(2-Cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo(2,3-a)pyrrolo(3,4-c)-carbazole; specific for conventional PKCs). In addition, sole activation of PKC using Phorbol 12-myristate 13-acetate (PMA) was sufficient for a synergistic interaction with EGF. In contrast to bradykinin however, PMA was mitogenic by itself which was not at all affected by Gö 6976, but abolished by GF 109203X. Bradykinin transiently activated the p42/p44 MAP kinase pathway, whereas PMA-induced activation of p42/p44 mitogen activated protein (MAP) kinase was sustained. Neither the combination of brad...Continue Reading

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Apr 6, 2004·European Journal of Pharmacology·Yaping ZhangLars-Olaf Cardell
Feb 8, 2005·American Journal of Respiratory and Critical Care Medicine·Reinoud GosensHerman Meurs
Jan 20, 2009·American Journal of Respiratory Cell and Molecular Biology·Nikita K MalaviaSteven C George

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Citations

May 11, 2006·Respiratory Research·Reinoud GosensAndrew J Halayko
Sep 20, 2012·Pulmonary Pharmacology & Therapeutics·Adrian R WestYnuk Bossé
Dec 31, 2008·Pulmonary Pharmacology & Therapeutics·Jeremy A HirotaThai Tran
Nov 27, 2007·European Journal of Pharmacology·Claudio ValentiCarlo Alberto Maggi
May 8, 2010·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·Y BosséM Rola-Pleszczynski
Apr 18, 2008·European Journal of Pharmacology·Reinoud GosensHerman Meurs
Sep 18, 2007·American Journal of Physiology. Lung Cellular and Molecular Physiology·Reinoud GosensAndrew J Halayko

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