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• W2084925375 abstract "Multiple lines of evidence indicate that serotonin (5-hydroxytryptamine [5-HT]) and voltage-gated K+ (KV) channels play a central role in the pathogenesis of pulmonary hypertension (PH). We hypothesized that 5-HT might modulate the activity of KV channels, therefore establishing a link between these pathogenetic factors in PH. Here, we studied the effects of 5-HT on KV channels present in rat pulmonary artery smooth muscle cells (PASMC) and on hKV1.5 channels stably expressed in Ltk- cells. 5-HT reduced native KV and hKV1.5 currents, depolarized cell membrane, and caused a contraction of isolated pulmonary arteries. The effects of 5-HT on KV currents and contraction were markedly prevented by the 5-HT2A receptor antagonist ketanserin. Incubation with inhibitors of phospholipase C (U73122), classic protein kinase Cs (Gö6976), or tyrosine kinases (genistein and tyrphostin 23), the cholesterol depletion agent beta-cyclodextrin or concanavalin A, an inhibitor of endocytotic processes, also prevented the effects of 5-HT. In homogenates from pulmonary arteries, 5-HT2A receptors and caveolin-1 coimmunoprecipitated with KV1.5 channels, and this was increased on stimulation with 5-HT. Moreover, KV1.5 channels were internalized when cells were stimulated with 5-HT, and this was prevented by concanavalin A. These findings indicate that activation of 5-HT2A receptors inhibits native KV and hKV1.5 currents via phospholipase C, protein kinase C, tyrosine kinase, and a caveolae pathway. KV channel inhibition accounts, at least partly, for 5-HT-induced pulmonary vasoconstriction and might play a role in PH." @default.
• W2084925375 created "2016-06-24" @default.
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• W2084925375 date "2006-04-14" @default.
• W2084925375 modified "2023-10-18" @default.
• W2084925375 title "Serotonin Inhibits Voltage-Gated K ⁺ Currents in Pulmonary Artery Smooth Muscle Cells" @default.
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• W2084925375 doi "https://doi.org/10.1161/01.res.0000216858.04599.e1" @default.
• W2084925375 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16527989" @default.
• W2084925375 hasPublicationYear "2006" @default.
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