Serotonin-stimulated increase in cytosolic Ca(2+) in cultured rat heart endothelial cells.
This study was designed to investigate the effects of serotonin on changes in intracellular Ca(2+) concentration ([Ca(2+)](i)) in cultured rat heart endothelial cells. Serotonin stimulated a biphasic change in cytosolic Ca(2+) of rat heart endothelial cells: an initial transient increase, which primarily reflects the release of Ca(2+) from internal stores, followed by a slow rise in [Ca(2+)](i) during the incubation with serotonin. Our study also demonstrated that the pattern of the serotonin-induced increase in [Ca(2+)](i) was different from that induced by thrombin in rat heart endothelial cells. In this study, the role of [Ca(2+)](i) on endothelial paracellular barrier function was also investigated. Serotonin induced an increase in endothelial permeability which paralleled the rise in [Ca(2+)](i) and was blocked by the 5-HT(2) receptor antagonist cyproheptadine. Therefore, the serotonin-stimulated increase in cytosolic Ca(2+) and macromolecular permeability was receptor-mediated in rat heart endothelial cells. Further experiments demonstrated that the serotonin-induced increase in [Ca(2+)](i) was inhibited by the phospholipase C inhibitors, neomycin and [6-[[17beta-3-methoxyestra-1,3, 5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U73122). Experiments involving the rapid depletion of intracellular Ca(2+) stores and Ca(2+)-free medium demonstrated that the biphasic response of endothelial Ca(2+) to serotonin was related to the release of Ca(2+) from intracellular stores and to the influx of extracellular Ca(2+). We also suggest that serotonin-induced changes in [Ca(2+)](i) are related to Ca(2+) channels sensitive to voltage-operated and inorganic Ca(2+) channel blockers.
Lee
H Z
HZ
School of Pharmacy, China Medical College, 91, Hsueh-Shih Road, Taichung, Taiwan.
Wu
C H
CH
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002417:Cattle; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D003600:Cytosol / Q000737:chemistry / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004963:Estrenes / Q000494:pharmacology; D005312:Fetal Blood / Q000378:metabolism; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D009355:Neomycin / Q000494:pharmacology; D009532:Nickel / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000494:pharmacology*; D013997:Time Factors; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004963:Estrenes; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D012701:Serotonin; C022838:nickel chloride; D009532:Nickel; D014700:Verapamil; D007770:L-Lactate Dehydrogenase; D010738:Type C Phospholipases; D009355:Neomycin; D002118:Calcium