Endothelin-1 decreases [Ca2+]i via Na+/Ca2+ exchanger in CHO cells stably expressing endothelin ETA receptor.
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概要
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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.
- 2007-07-02
著者
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Miwa Soichi
Department Of Cellular Pharmacology Hokkaido University Graduate School Of Medicine
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Horinouchi Takahiro
北海道大学 医学研究科細胞薬理学分野
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Miwa Soichi
Division Of Pharmacology Department Of Biochemistry And Bioinformative Sciences School Of Medicine U
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Kajita Emi
Department Of Cellular Pharmacology Hokkaido University Graduate School Of Medicine
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Miwa Soichi
Dep. Of Cellular Pharmacology Hokkaido Univ. Graduate School Of Medicine Jpn
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Morishima Shigeru
Division Of Pharmacology Department Of Biochemistry And Bioinformative Sciences School Of Medicine U
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Horinouchi Takahiro
Department Of Cellular Pharmacology Hokkaido University Graduate School Of Medicine
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Nishimoto Arata
Department Of Cellular Pharmacology Hokkaido University Graduate School Of Medicine
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Nishiya Tadashi
Department Of Cellular Pharmacology Hokkaido University Graduate School Of Medicine
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Horinouchi Takahiro
Department Of Cellular Pharmacology Graduate School Of Medicine Hokkaido University
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