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• W2105188846 abstract "Serotonin (5-hydroxytryptamine, 5-HT) is a vasoconstrictor and mitogen whose levels are elevated in diabetes. Previous studies have shown the presence of 5-HT 2A , 5-HT 2B , and 5-HT 1B receptors in vascular smooth muscle cells (VSMCs). There are currently no data regarding 5-HT 2B and 5-HT 1B receptor activation of the JAK/STAT pathway in VSMCs and resultant potential alterations in 5-HT signaling in diabetes. Therefore, we tested the hypothesis that 5-HT differentially activates the JAK/STAT pathway in VSMCs under conditions of normal (5 mM) and high (25 mM) glucose. Treatment of rat VSMCs with 5-HT (10 −6 M) resulted in time-dependent activation (∼2-fold) of JAK2, JAK1, and STAT1, but not STAT3 (maximal at 5 min, returned to baseline by 30 min). The 5-HT 2B receptor agonist BW723C86 and the 5-HT 1B receptor agonist CGS12066A (10 −9 –10 −5 M, 5-min stimulation) did not activate the JAK/STAT pathway. Treatment with the 5-HT 2A receptor antagonist ketanserin (10 nM) inhibited JAK2 activation by 5-HT. Treatment of streptozotocin-induced diabetic rats with ketanserin (5 mg·kg −1 ·day −1 ) reduced activation of JAK2 and STAT1 but not STAT3 in endothelium-denuded thoracic aorta in vivo. 5-HT (10 −6 M) treatment resulted in increased cell proliferation and increased DNA synthesis, which were inhibited by the JAK2 inhibitor AG490. Further studies with apocynin, diphenyleneiodonium chloride, catalase, and virally transfected superoxide dismutase had no effect at either glucose concentration on activation of the JAK/STAT pathway by 5-HT. Therefore, we conclude that 5-HT activates JAK2, JAK1, and STAT1 via the 5-HT 2A receptors in a reactive oxygen species-independent manner under both normal and high glucose conditions." @default.
• W2105188846 created "2016-06-24" @default.
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• W2105188846 date "2005-04-01" @default.
• W2105188846 modified "2023-10-16" @default.
• W2105188846 title "Activation of the JAK/STAT pathway in vascular smooth muscle by serotonin" @default.
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• W2105188846 doi "https://doi.org/10.1152/ajpcell.00385.2004" @default.
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