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.