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

Autor: Anita ten Damme, Herman Meurs, Johan Zaagsma, Reinoud Gosens, Harm Maarsingh, S. Adriaan Nelemans, Mechteld M. Grootte Bromhaar
Přispěvatelé: Groningen Research Institute for Asthma and COPD (GRIAC), Molecular Pharmacology
Rok vydání: 2005
Předmět:
Platelet-derived growth factor
Indoles
Receptor
Bradykinin B2
Mitogen-Activated Protein Kinase 3
DNA-SYNTHESIS
CYCLIC-AMP
TGF-beta (transforming growth factor-beta)
ASTHMATIC SUBJECTS
Maleimides
chemistry.chemical_compound
airway remodeling
Epidermal growth factor
Enzyme Inhibitors
Cells
Cultured
Protein Kinase C
Mitogen-Activated Protein Kinase 1
Kinase
Drug Synergism
Cell biology
Isoenzymes
Trachea
PDGF (platelet-derived growth factor)
Tetradecanoylphorbol Acetate
BRONCHIAL-ASTHMA
HOE 140
medicine.medical_specialty
Myocytes
Smooth Muscle
Carbazoles
Bradykinin
G protein coupled receptor
Biology
Tritium
CELL-PROLIFERATION
Internal medicine
medicine
Animals
Bradykinin receptor
Protein kinase C
Cell Proliferation
Pharmacology
Dose-Response Relationship
Drug
Epidermal Growth Factor
ADENYLATE-CYCLASE
IN-VITRO
asthma
SYNERGISTIC STIMULATION
Enzyme Activation
Endocrinology
chemistry
Phorbol
GUINEA-PIG TRACHEA
Cattle
Thymidine
Zdroj: European Journal of Pharmacology, 535(1-3), 253-262. ELSEVIER SCIENCE BV
ISSN: 0014-2999
Popis: 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 [H-3]thymidine incorporation and cell proliferation. The bradykinin effect was mediated by bradykinin B? 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 1; specific for conventional and novel PKCs) and Go 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 Go 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 bradykinin and EGF nor that of PMA and EGF induced synergistic activation of p42/p44 MAP kinase, however. These results show that bradykinin B, receptor-stimulation augments growth factor-induced mitogenic responses of airway smooth muscle cells through activation of conventional PKC isozymes. In addition, the results show that PKC isozyme-specificity underlies stimulus-specific differences in mitogenic capacity for bradykinin and PMA. Published by Elsevier B.V.
Databáze: OpenAIRE
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