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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Hayasaki-kajiwara, Y. Naya, N. Iwasaki, T. Shimamura, T. Nakajima, M. |
| Description | Author Affiliation: Hayasaki-Kajiwara Y ( Discovery Research Laboratories, Shionogi & Co., Ltd., Toyonaka, Osaka, Japan.) |
| Abstract | The effects of endothelin (ET)-1(1-31) and ET-2(1-31), human chymase products of the corresponding big ETs, on the intracellular free Ca2+ concentration ([Ca2+]i) and [125I]-ET-1 binding were investigated using human cultured bronchial smooth muscle cells (BSMC). ET-1(1-31) (10(-8)M - 3 x 10(-7)M) and ET-2(1-31) (3 x 10(-8)M - 3 x 10(-6) M) caused an increase in [Ca2+]i in a concentration-dependent manner. Big ET-1 (3 x 10(-8)M - 10(-6)M) also caused this increase, but not big ET-2 at concentrations up to 10(-6)M. The [Ca2+]i increase induced by ET-1 was inhibited by both BQ123, an ET(A)-receptor antagonist, and BQ788, an ET(B)-receptor antagonist, whereas that induced by ET-3 was inhibited by BQ788 but not by BQ123. Increases in [Ca2+]i caused by ET-1(1-31), big ET-1 and ET-2(1-31) were completely inhibited by 10(-4)M phosphoramidon, a dual neutral endopeptidase (NEP)/endothelin-converting enzyme (ECE) inhibitor, and 10(-5)M thiorphan, a NEP inhibitor. Scatchard plot analyses of the saturation curves of [125I]-ET-1 and [125I]-ET-3 showed that both ET(A)- and ET(B)- receptors at the ratio of 4:1 were expressed on BSMC. ET-1(1-31), big ET-1 and ET-2(1-31) inhibited [125I]-ET-1 binding in a concentration-dependent manner, and these effects were attenuated by treatment with thiorphan. On the other hand, big ET-2 slightly inhibited the binding at a high concentration and this was not affected by thiorphan. These results suggest that ET-1(1-31), big ET-1 and ET-2(1-31) cause an increase in [Ca2+]i by being converted into the corresponding ET-1 and ET-2 by NEP, but this did not occur with big ET-2 in human BSMC. ET-2(1-31), produced by human chymase from big ET-2 might be important for the generation of ET-2 in human bronchial tissue. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 6 |
| Volume Number | 127 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1999-07-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Bronchi Drug Effects Endothelins Pharmacology Muscle, Smooth Peptide Fragments Binding, Competitive Cytology Metabolism Calcium Cells, Cultured Endothelin-1 Endothelin-3 Chemistry Glycopeptides Iodine Radioisotopes Oligopeptides Peptides, Cyclic Piperidines Protease Inhibitors Radioligand Assay Receptor, Endothelin A Receptor, Endothelin B Receptors, Endothelin Biosynthesis |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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