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- W2317695933 abstract "Urotensin II (U-II), the most potent vasoconstrictor, and serotonin (5-HT) are known to play an important role in pulmonary hypertension. However, little is known about the effect of U-II and its interaction with 5-HT on vascular smooth muscle cell (VSMC) proliferation.We assessed the interaction between U-II and 5-HT in inducing VSMC proliferation.Growth-arrested rabbit VSMCs were incubated in serum-free medium with different concentrations of U-II and 5-HT. VSMC proliferation was examined by the increase in [3H]thymidine incorporation into DNA and cell number.U-II or 5-HT induced [3H]thymidine incorporation in a dose-dependent manner with a maximal effect at a concentration of 50 nmol/l (161%) or 50 micromol/l (205%), respectively. When added together, low concentrations of U-II (50 nmol/l) and 5-HT (1 micromol/l) interacted synergistically in inducing [3H]thymidine incorporation (382%). These effects on [3H]thymidine incorporation were paralleled by an increase in cell number. The G-protein inactivator GDP-beta-S (100 micromol/l), protein kinase C (PKC) inhibitor Ro31-8220 (0.1 micromol/l), Src family tyrosine kinase inhibitor PP2 (1 micromol/l), and mitogen-activated protein kinase (MAPK) kinase inhibitor PD098059 (10 micromol/l) inhibited the mitogenic effects of U-II and 5-HT and also their interaction in inducing [3H]thymidine incorporation.Our results suggest that U-II and 5-HT may induce the synergistic interaction in inducing VSMC proliferation via a G-protein-coupled receptor/PKC/Src tyrosine kinase/MAPK pathway, thus contributing to the relatively rapid development of atherosclerosis in hypertensive vascular disease." @default.
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- W2317695933 date "2001-12-01" @default.
- W2317695933 modified "2023-10-16" @default.
- W2317695933 title "Synergistic effect of urotensin II with serotonin on vascular smooth muscle cell proliferation" @default.
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- W2317695933 doi "https://doi.org/10.1097/00004872-200112000-00012" @default.
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