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Endothelin-1 decreases [Ca2+]i via Na+/Ca2+ exchanger in CHO cells stably expressing endothelin ETA receptor.
Title: | Endothelin-1 decreases [Ca2+]i via Na+/Ca2+ exchanger in CHO cells stably expressing endothelin ETA receptor. |
Authors: | Horinouchi, Takahiro Browse this author →KAKEN DB | Nishimoto, Arata Browse this author →KAKEN DB | Nishiya, Tadashi Browse this author | Lu, Lingyun Browse this author | Kajita, Emi Browse this author | Miwa, Soichi Browse this author |
Keywords: | Endothelin-1 | Endothelin receptor | Gq/11 protein | Na+/Ca2+ exchanger | Intracellular free Ca2+ concentration |
Issue Date: | 2-Jul-2007 |
Publisher: | Elsevier |
Journal Title: | European Journal of Pharmacology |
Volume: | 566 |
Issue: | 1-3 |
Start Page: | 28 |
End Page: | 33 |
Publisher DOI: | 10.1016/j.ejphar.2007.03.019 |
PMID: | 17445794 |
Abstract: | Endothelin ETA receptor couples to Gq/11 protein that transduces a variety of receptor signals to modulate diverse cellular responses including Ca2+ mobilization. Stimulation of endothelin ETA receptor with endothelin-1 is generally believed to induce an increase in intracellular Ca2+ concentration ([Ca2+]i) via Gq/11 protein. Here we provide the first convincing evidence that endothelin-1 elicited Gq/11 protein-dependent and -independent ‘decrease’ in [Ca2+]i via Na+/Ca2+ exchanger (NCX) in Chinese hamster ovary (CHO) cells stably expressing human endothelin ETA receptor. In the cells treated with 1 μM thapsigargin, an inhibitor of endoplasmic Ca2+ pump, that induces an increase in [Ca2+]i via capacitative Ca2+ entry, endothelin-1 induced a decrease in [Ca2+]i which was partially inhibited by YM-254890, a specific inhibitor of Gq/11, indicating that Gq/11-dependent and independent pathways are involved in the decrease. The endothelin-1-induced decrease in [Ca2+]i was markedly suppressed by 3′,4′-dichlorobenzamil hydrochloride, a potent NCX inhibitor, and also by a replacement of extracellular Na+ with Li+, which was not transported by NCX, indicating a major role of NCX operating in the forward mode in the endothelin-1-induced decrease in [Ca2+]i. Molecular approach with RT-PCR demonstrated the expression of mRNA for NCX1, NCX2 and NCX3. These results suggest that stimulation of endothelin ETA receptor with endothelin-1 activates the forward mode NCX through Gq/11-dependent and -independent mechanisms: the NCX exports Ca2+ out of the cell depending on Na+ gradient across the cell membrane, resulting in the decrease in [Ca2+]i. |
Relation: | http://www.sciencedirect.com/science/journal/00142999 |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/28203 |
Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 三輪 聡一
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