Serotonin-stimulated increase in cytosolic Ca2+ in cultured rat heart endothelial cells

Authors
Citation
Hz. Lee et Ch. Wu, Serotonin-stimulated increase in cytosolic Ca2+ in cultured rat heart endothelial cells, EUR J PHARM, 384(1), 1999, pp. 53-60
Citations number
27
Categorie Soggetti
Pharmacology & Toxicology
Journal title
EUROPEAN JOURNAL OF PHARMACOLOGY
ISSN journal
00142999 → ACNP
Volume
384
Issue
1
Year of publication
1999
Pages
53 - 60
Database
ISI
SICI code
0014-2999(19991112)384:1<53:SIICCI>2.0.ZU;2-3
Abstract
This study was designed to investigate the effects of serotonin on changes in intracellular Ca2+ concentration ([Ca2+](i)) in cultured rat heart endot helial cells. Serotonin stimulated a biphasic change in cytosolic Ca2+ of r at heart endothelial cells: an initial transient increase, which primarily reflects the release of Ca2+ from internal stores, followed by a slow rise in [Ca2+](i) during the incubation with serotonin. Our study also demonstra ted that the pattern of the serotonin-induced increase in [Ca2+](i) was dif ferent from that induced by thrombin in rat heart endothelial cells. In thi s study, the role of [Ca2+](i) on endothelial paracellular barrier function was also investigated. Serotonin induced an increase in endothelial permea bility which paralleled the rise in [Ca2+](i) and was blocked by the 5-HT2 receptor antagonist cyproheptadine. Therefore, the serotonin-stimulated inc rease in cytosolic Ca2+ and macromolecular permeability was receptor-mediat ed in rat heart endothelial cells. Further experiments demonstrated that th e serotonin-induced increase in [Ca2+](i) was inhibited by the phospholipas e C inhibitors, neomycin and [6-[[17 beta-3-methoxyestra-1,3,5(10)-trien-17 -yl]amino]hexyl]-1H-pyrrole-2,5-dione (U73122). Experiments involving the r apid depletion of intracellular Ca2+ stores and Ca2+-free medium demonstrat ed that the biphasic response of endothelial Ca2+ to serotonin was related to the release of Ca2+ from intracellular stores and to the influx of extra cellular Ca2+. We also suggest that serotonin-induced changes in [Ca2+](i) are related to Ca2+ channels sensitive to voltage-operated and inorganic Ca 2+ channel blockers. (C) 1999 Elsevier Science B.V. All rights reserved.