P2Y Receptor-Mediated Ca2+ Signaling Increases Human Vascular Endothelial Cell Permeability
We investigated the effects of P2-receptor agonists on cell size, intracellular calcium levels ([Ca2+]i), and permeation of FITC-labeled dextran (FD-4) as well as the relationship between these effects in human umbilical vein endothelial cells (HUVEC). FD-4 concentration, cell size, and [Ca2+]i were...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2004-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S134786131932434X |
| _version_ | 1811266066743033856 |
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| author | Naoko Tanaka Kumiko Kawasaki Namie Nejime Yoko Kubota Kazuki Nakamura Masaru Kunitomo Koichi Takahashi Michio Hashimoto Kazumasa Shinozuka |
| author_facet | Naoko Tanaka Kumiko Kawasaki Namie Nejime Yoko Kubota Kazuki Nakamura Masaru Kunitomo Koichi Takahashi Michio Hashimoto Kazumasa Shinozuka |
| author_sort | Naoko Tanaka |
| collection | DOAJ |
| description | We investigated the effects of P2-receptor agonists on cell size, intracellular calcium levels ([Ca2+]i), and permeation of FITC-labeled dextran (FD-4) as well as the relationship between these effects in human umbilical vein endothelial cells (HUVEC). FD-4 concentration, cell size, and [Ca2+]i were analyzed by HPLC with fluorescence, phase contrast microscopic imaging, and fluorescent confocal microscopic imaging, respectively. The P2Y1-receptor agonists 2-methylthio ATP (2meS-ATP) and ADP decreased cell size and increased [Ca2+]i in HUVEC. The P2Y2-receptor agonist UTP increased [Ca2+]i, but did not influence cell size. The P2X-receptor agonist α,β-methylene ATP did not induce either response. The decrease in size and increase in [Ca2+]i by 2meS-ATP were blocked by pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS, P2Y1-antagonist), thapsigargin (Ca2+-pump inhibitor), and U73122 (phospholipase C inhibitor). Furthermore, 2meS-ATP (P2Y1-receptor agonist) enhanced permeation of FD-4 through the endothelial cell monolayer. The 2meS-ATP-induced enhancement of the permeation was also prevented by PPADS, thapsigargin, and U73122. These results indicate that activation of P2Y receptors induces a decrease in cell size, an increase in [Ca2+]i, and may participate in facilitating macromolecular permeability in HUVEC. Keywords:: cell size, intracellular Ca2+, permeability, P2Y receptor, human umbilical vein endothelial cell |
| first_indexed | 2024-04-12T20:35:23Z |
| format | Article |
| id | doaj.art-d5475add338f4cb18531da2fad829fb1 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-04-12T20:35:23Z |
| publishDate | 2004-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-d5475add338f4cb18531da2fad829fb12022-12-22T03:17:36ZengElsevierJournal of Pharmacological Sciences1347-86132004-01-01952174180P2Y Receptor-Mediated Ca2+ Signaling Increases Human Vascular Endothelial Cell PermeabilityNaoko Tanaka0Kumiko Kawasaki1Namie Nejime2Yoko Kubota3Kazuki Nakamura4Masaru Kunitomo5Koichi Takahashi6Michio Hashimoto7Kazumasa Shinozuka8Departments of Pharmacology, Mukogawa Women’s University, Nishinomiya 663-8179, JapanDepartments of Pharmacology, Mukogawa Women’s University, Nishinomiya 663-8179, JapanDepartments of Pharmacology, Mukogawa Women’s University, Nishinomiya 663-8179, JapanDepartments of Pharmacology, Mukogawa Women’s University, Nishinomiya 663-8179, JapanDepartments of Pharmacology, Mukogawa Women’s University, Nishinomiya 663-8179, JapanDepartments of Pharmacology, Mukogawa Women’s University, Nishinomiya 663-8179, JapanDepartments of Pharmaceutics, School of Pharmaceutical Sciences, Mukogawa Women’s University, Nishinomiya 663-8179, JapanDepartment of Physiology, Shimane Medical University, Izumo, Shimane 693-8501, JapanDepartments of Pharmacology, Mukogawa Women’s University, Nishinomiya 663-8179, Japan; Corresponding author. FAX: +81-798-41-2792 E-mail: kazumasa@mwu.mukogawa-u.ac.jpWe investigated the effects of P2-receptor agonists on cell size, intracellular calcium levels ([Ca2+]i), and permeation of FITC-labeled dextran (FD-4) as well as the relationship between these effects in human umbilical vein endothelial cells (HUVEC). FD-4 concentration, cell size, and [Ca2+]i were analyzed by HPLC with fluorescence, phase contrast microscopic imaging, and fluorescent confocal microscopic imaging, respectively. The P2Y1-receptor agonists 2-methylthio ATP (2meS-ATP) and ADP decreased cell size and increased [Ca2+]i in HUVEC. The P2Y2-receptor agonist UTP increased [Ca2+]i, but did not influence cell size. The P2X-receptor agonist α,β-methylene ATP did not induce either response. The decrease in size and increase in [Ca2+]i by 2meS-ATP were blocked by pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS, P2Y1-antagonist), thapsigargin (Ca2+-pump inhibitor), and U73122 (phospholipase C inhibitor). Furthermore, 2meS-ATP (P2Y1-receptor agonist) enhanced permeation of FD-4 through the endothelial cell monolayer. The 2meS-ATP-induced enhancement of the permeation was also prevented by PPADS, thapsigargin, and U73122. These results indicate that activation of P2Y receptors induces a decrease in cell size, an increase in [Ca2+]i, and may participate in facilitating macromolecular permeability in HUVEC. Keywords:: cell size, intracellular Ca2+, permeability, P2Y receptor, human umbilical vein endothelial cellhttp://www.sciencedirect.com/science/article/pii/S134786131932434X |
| spellingShingle | Naoko Tanaka Kumiko Kawasaki Namie Nejime Yoko Kubota Kazuki Nakamura Masaru Kunitomo Koichi Takahashi Michio Hashimoto Kazumasa Shinozuka P2Y Receptor-Mediated Ca2+ Signaling Increases Human Vascular Endothelial Cell Permeability Journal of Pharmacological Sciences |
| title | P2Y Receptor-Mediated Ca2+ Signaling Increases Human Vascular Endothelial Cell Permeability |
| title_full | P2Y Receptor-Mediated Ca2+ Signaling Increases Human Vascular Endothelial Cell Permeability |
| title_fullStr | P2Y Receptor-Mediated Ca2+ Signaling Increases Human Vascular Endothelial Cell Permeability |
| title_full_unstemmed | P2Y Receptor-Mediated Ca2+ Signaling Increases Human Vascular Endothelial Cell Permeability |
| title_short | P2Y Receptor-Mediated Ca2+ Signaling Increases Human Vascular Endothelial Cell Permeability |
| title_sort | p2y receptor mediated ca2 signaling increases human vascular endothelial cell permeability |
| url | http://www.sciencedirect.com/science/article/pii/S134786131932434X |
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