Abstract |
Thromboxane A2 receptor (TP) mediates bronchial smooth muscle cell (BSMC) contraction, airway hyperresponsiveness, and airway inflammation in patients with asthma. In the present study, a pathogenic role of TP activation in airway remodeling was examined using primary cultures of human BSMC. A TP agonist, I-BOP, concentration-dependently enhanced not only bromodeoxyuridine ( BrdU) uptake but also cell proliferation of BSMC. A TP-selective antagonist, AA-2414, blocked the effects of I-BOP on both BrdU uptake and cell proliferation. I-BOP-induced BrdU uptake was significantly blocked by two non-selective tyrosine kinase inhibitors, genistein and herbimycin A, or a Src family tyrosine kinase inhibitor, PP2, but not by an inhibitor of epidermal growth factor ( EGF) receptor-associated tyrosine kinase, AG1478. In conclusion, TP receptor activation causes DNA synthesis and cell proliferation of human BSMC by activating tyrosine kinases including Src, but not by EGF receptor transactivation.
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Authors | Yusuke Suzuki, Koichiro Asano, Yoshiki Shiraishi, Tsuyoshi Oguma, Tetsuya Shiomi, Koichi Fukunaga, Takeshi Nakajima, Kyoko Niimi, Kazuhiro Yamaguchi, Akitoshi Ishizaka |
Journal | Prostaglandins, leukotrienes, and essential fatty acids
(Prostaglandins Leukot Essent Fatty Acids)
Vol. 71
Issue 6
Pg. 375-82
(Dec 2004)
ISSN: 0952-3278 [Print] Scotland |
PMID | 15519496
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Bridged Bicyclo Compounds, Heterocyclic
- Fatty Acids, Unsaturated
- Intracellular Signaling Peptides and Proteins
- Receptors, Thromboxane A2, Prostaglandin H2
- protein kinase modulator
- 7-(3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl)-7-oxabicyclo(2.2.1)heptan-2-yl)-5-heptenoic acid
- Epidermal Growth Factor
- Protein-Tyrosine Kinases
- Bromodeoxyuridine
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Topics |
- Bridged Bicyclo Compounds, Heterocyclic
(agonists)
- Bromodeoxyuridine
(pharmacology)
- Bronchi
(cytology)
- Cell Proliferation
(drug effects)
- Cells, Cultured
- Epidermal Growth Factor
(pharmacology)
- Fatty Acids, Unsaturated
(agonists)
- Humans
- Intracellular Signaling Peptides and Proteins
(pharmacology)
- Muscle, Smooth
(cytology, drug effects, metabolism)
- Phosphorylation
(drug effects)
- Protein-Tyrosine Kinases
(antagonists & inhibitors, metabolism)
- Receptors, Thromboxane A2, Prostaglandin H2
(metabolism)
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