Lafutidine-Induced Increase in Intracellular Ca2+ Concentrations in PC12 and Endothelial Cells
Lafutidine, a histamine H2 receptor antagonist, exerts gastroprotective effects in addition to gastric antisecretory activity. The gastrointestinal protective effects of lafutidine are mediated by capsaicin-sensitive neurons, where capsaicin excites neurons by opening a member of the transient recep...
| Hlavní autoři: | , , , , |
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| Médium: | Článek |
| Jazyk: | English |
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Elsevier
2005-01-01
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| Edice: | Journal of Pharmacological Sciences |
| On-line přístup: | http://www.sciencedirect.com/science/article/pii/S1347861319322959 |
| _version_ | 1828236625480515584 |
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| author | Kana Kunieda Akiyoshi Someya Syunji Horie Hirofusa Ajioka Toshihiko Murayama |
| author_facet | Kana Kunieda Akiyoshi Someya Syunji Horie Hirofusa Ajioka Toshihiko Murayama |
| author_sort | Kana Kunieda |
| collection | DOAJ |
| description | Lafutidine, a histamine H2 receptor antagonist, exerts gastroprotective effects in addition to gastric antisecretory activity. The gastrointestinal protective effects of lafutidine are mediated by capsaicin-sensitive neurons, where capsaicin excites neurons by opening a member of the transient receptor potential channel family (TRPV1). Since the effect of lafutidine on the intracellular Ca2+ concentration ([Ca2+]i) in cells has not been elucidated, we investigated the lafutidine response to [Ca2+]i in rat pheochromocytoma PC12 and human endothelial cells. Lafutidine at pharmacological concentrations greater than 1 mM induced a sustained increase in [Ca2+]i in the presence of extracellular CaCl2 in PC12 cells, while capsaicin showed dual effects on [Ca2+]i in PC12 cells, where it activated TRPV1 and inhibited store-operated Ca2+ entry. The thapsigargin (an activator of store-operated Ca2+ entry)-induced increase in [Ca2+]i in PC12 cells was inhibited by capsaicin and SKF96365, an inhibitor of store-operated Ca2+ entry, and the lafutidine response was inhibited by capsaicin but not by SKF96365. In endothelial cells, lafutidine induced an increase in [Ca2+]i in a SKF96365-insensitive manner. These results suggest that lafutidine stimulates Ca2+ entry via the capsaicin-sensitive pathway but not the SKF96365-sensitive pathway. The possible role of store-operated Ca2+ entry induced by lafutidine on gastrointestinal function is also discussed. Keywords:: lafutidine, intracellular Ca2+ concentration, PC12 cell, human umbilical vein endothelial cell, store-operated Ca2+ entry |
| first_indexed | 2024-04-12T20:35:37Z |
| format | Article |
| id | doaj.art-06b0c25a6d1c44b594d8df5fab6bbb3c |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-04-12T20:35:37Z |
| publishDate | 2005-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-06b0c25a6d1c44b594d8df5fab6bbb3c2022-12-22T03:17:36ZengElsevierJournal of Pharmacological Sciences1347-86132005-01-019716774Lafutidine-Induced Increase in Intracellular Ca2+ Concentrations in PC12 and Endothelial CellsKana Kunieda0Akiyoshi Someya1Syunji Horie2Hirofusa Ajioka3Toshihiko Murayama4Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, JapanLaboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, JapanLaboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, JapanTokushima Research Center, Taiho Pharmaceutical Co., Ltd., Kawauchi-cho, Tokushima 771-0194, JapanLaboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan; Corresponding author. FAX: +81-43-226-2875 E-mail: murayama@p.chiba-u.ac.jpLafutidine, a histamine H2 receptor antagonist, exerts gastroprotective effects in addition to gastric antisecretory activity. The gastrointestinal protective effects of lafutidine are mediated by capsaicin-sensitive neurons, where capsaicin excites neurons by opening a member of the transient receptor potential channel family (TRPV1). Since the effect of lafutidine on the intracellular Ca2+ concentration ([Ca2+]i) in cells has not been elucidated, we investigated the lafutidine response to [Ca2+]i in rat pheochromocytoma PC12 and human endothelial cells. Lafutidine at pharmacological concentrations greater than 1 mM induced a sustained increase in [Ca2+]i in the presence of extracellular CaCl2 in PC12 cells, while capsaicin showed dual effects on [Ca2+]i in PC12 cells, where it activated TRPV1 and inhibited store-operated Ca2+ entry. The thapsigargin (an activator of store-operated Ca2+ entry)-induced increase in [Ca2+]i in PC12 cells was inhibited by capsaicin and SKF96365, an inhibitor of store-operated Ca2+ entry, and the lafutidine response was inhibited by capsaicin but not by SKF96365. In endothelial cells, lafutidine induced an increase in [Ca2+]i in a SKF96365-insensitive manner. These results suggest that lafutidine stimulates Ca2+ entry via the capsaicin-sensitive pathway but not the SKF96365-sensitive pathway. The possible role of store-operated Ca2+ entry induced by lafutidine on gastrointestinal function is also discussed. Keywords:: lafutidine, intracellular Ca2+ concentration, PC12 cell, human umbilical vein endothelial cell, store-operated Ca2+ entryhttp://www.sciencedirect.com/science/article/pii/S1347861319322959 |
| spellingShingle | Kana Kunieda Akiyoshi Someya Syunji Horie Hirofusa Ajioka Toshihiko Murayama Lafutidine-Induced Increase in Intracellular Ca2+ Concentrations in PC12 and Endothelial Cells Journal of Pharmacological Sciences |
| title | Lafutidine-Induced Increase in Intracellular Ca2+ Concentrations in PC12 and Endothelial Cells |
| title_full | Lafutidine-Induced Increase in Intracellular Ca2+ Concentrations in PC12 and Endothelial Cells |
| title_fullStr | Lafutidine-Induced Increase in Intracellular Ca2+ Concentrations in PC12 and Endothelial Cells |
| title_full_unstemmed | Lafutidine-Induced Increase in Intracellular Ca2+ Concentrations in PC12 and Endothelial Cells |
| title_short | Lafutidine-Induced Increase in Intracellular Ca2+ Concentrations in PC12 and Endothelial Cells |
| title_sort | lafutidine induced increase in intracellular ca2 concentrations in pc12 and endothelial cells |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319322959 |
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