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Dive into the research topics where Laura Cobeno is active.

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Featured researches published by Laura Cobeno.


Circulation Research | 2006

Serotonin Inhibits Voltage-Gated K+ Currents in Pulmonary Artery Smooth Muscle Cells: Role of 5-HT2A Receptors, Caveolin-1, and KV1.5 Channel Internalization

Angel Cogolludo; Laura Moreno; Federica Lodi; Giovanna Frazziano; Laura Cobeno; Juan Tamargo; Francisco Perez-Vizcaino

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 β-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.


Annals of the New York Academy of Sciences | 2006

Role of Reactive Oxygen Species in Kv Channel Inhibition and Vasoconstriction Induced by TP Receptor Activation in Rat Pulmonary Arteries

Angel Cogolludo; Giovanna Frazziano; Laura Cobeno; Laura Moreno; Federica Lodi; Eduardo Villamor; Juan Tamargo; Francisco Perez-Vizcaino

Abstract:u2002 Voltage‐gated potassium channels (Kv) and thromboxane A2 (TXA2) have been involved in several forms of human and experimental pulmonary hypertension. We have reported that the TXA2 analog U46619, via activation of TP receptors and PKCζ, inhibited Kv currents in rat pulmonary artery smooth muscle cells (PASMC), increased cytosolic calcium, and induced a contractile response in isolated rat and piglet pulmonary arteries (PA). Herein, we have analyzed the role of reactive oxygen species (ROS) in this signaling pathway. In rat PA, U46619 increased dichlorofluorescein fluorescence, an indicator of intracellular hydrogen peroxide, and this effect was prevented by the NADPH oxidase inhibitor apocynin and by polyethyleneglycol‐catalase (PEG‐catalase, a membrane‐permeable form of catalase). U46619 inhibited Kv currents in native PASMC and these effects were strongly inhibited by apocynin. The contractile responses to U46619 in isolated PA were inhibited by PEG‐catalase and the NADPH oxidase inhibitors diphenylene iodonium (DPI) and apocynin. A membrane permeable of hydrogen peroxide, t‐butyl hydroperoxide, also inhibited Kv currents and induced a contractile response. Activation of NADPH oxidase and the subsequent production of hydrogen peroxide are involved in the Kv channel inhibition and the contractile response induced by TP receptor activation in rat PA.


Molecular Pharmacology | 2007

Role of Protein Kinase Cζ and Its Adaptor Protein p62 in Voltage-Gated Potassium Channel Modulation in Pulmonary Arteries

Laura Moreno; Giovanna Frazziano; Angel Cogolludo; Laura Cobeno; Juan Tamargo; Francisco Perez-Vizcaino

Voltage-gated potassium (KV) channels play an essential role in regulating pulmonary artery function, and they underpin the phenomenon of hypoxic pulmonary vasoconstriction. Pulmonary hypertension is characterized by inappropriate vasoconstriction, vascular remodeling, and dysfunctional KV channels. In the current study, we aimed to elucidate the role of PKCζ and its adaptor protein p62 in the modulation of KV channels. We report that the thromboxane A2 analog 9,11-dideoxy-11α,9α-epoxymethano-prostaglandin F2α methyl acetate (U46619) inhibited KV currents in isolated mice pulmonary artery myocytes and the KV current carried by human cloned KV1.5 channels expressed in Ltk– cells. Using protein kinase C (PKC)ζ–/– and p62–/– mice, we demonstrate that these two proteins are involved in the KV channel inhibition. PKCζ coimmunoprecipitated with KV1.5, and this interaction was markedly reduced in p62–/– mice. Pulmonary arteries from PKCζ–/– mice also showed a diminished [Ca2+]i and contractile response, whereas genetic inactivation of p62–/– resulted in an absent [Ca2+]i response, but it preserved contractile response to U46619. These data demonstrate that PKCζ and its adaptor protein p62 play a key role in the modulation of KV channel function in pulmonary arteries. These observations identify PKCζ and/or p62 as potential therapeutic targets for the treatment of pulmonary hypertension.


Cardiovascular Research | 2007

The dietary flavonoid quercetin activates BKCa currents in coronary arteries via production of H2O2. Role in vasodilatation.

Angel Cogolludo; Giovanna Frazziano; Ana M. Briones; Laura Cobeno; Laura Moreno; Federica Lodi; Mercedes Salaices; Juan Tamargo; Francisco Perez-Vizcaino


The FASEB Journal | 2008

Role of voltage-gated potassium channels in the response to oxygen in chicken embryo ductus arteriosus

Laura Cobeno; Eduardo Villamor; Angel Cogolludo; Giovanna Frazziano; Javier Moral; Bea Zoer; Laura Moreno; Francisco Perez-Vizcaino


The FASEB Journal | 2007

Involvement of reactive oxygen species in Kv channels inhibition induced by hypoxia in rat pulmonary arteries

Giovanna Frazziano; Angel Cogolludo; Laura Moreno; Federica Lodi; Laura Cobeno; Juan Tamargo; Francisco Perez-Vizcaino


The FASEB Journal | 2007

Hydrogen peroxide mimics the responses to oxygen in chicken ductus arteriosus

Angel Cogolludo; Pia Ågren; Saskia van der Sterren; Carlos E Blanco; Laura Cobeno; Giovanna Frazziano; Francisco Perez-Vizcaino; Eduardo Villamor


The FASEB Journal | 2008

Ceramide induces inhibition of Kv channels and vasoconstriction in rat pulmonary arteries

Giovanna Frazziano; Laura Cobeno; Angel Cogolludo; Laura Moreno; Javier Moral; Eduardo Villamor; Francisco Perez-Vizcaino


The FASEB Journal | 2008

Neutral sphingomyelinase and protein kinase C{zeta} are involved in hypoxic pulmonary vasoconstriction

Angel Cogolludo; Laura Moreno; Laura Cobeno; Giovanna Frazziano; Javier Castañeda; C. Gonzalez; Eduardo Villamor; Francisco Perez-Vizcaino


The FASEB Journal | 2008

Increased activation of BKCa channels prevents endothelial dysfunction in coronary arteries from ouabain-induced hypertensive rats

Ana M. Briones; Laura Cobeno; Alessandra Simão Padilha; Angel Cogolludo; Dalton Valentim Vassallo; Francisco Perez-Vizcaino; Mercedes Salaices

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Francisco Perez-Vizcaino

Complutense University of Madrid

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Angel Cogolludo

Complutense University of Madrid

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Giovanna Frazziano

Complutense University of Madrid

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Laura Moreno

Complutense University of Madrid

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Federica Lodi

Complutense University of Madrid

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Juan Tamargo

Complutense University of Madrid

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Ana M. Briones

Autonomous University of Madrid

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Mercedes Salaices

Autonomous University of Madrid

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C. Gonzalez

University of Valladolid

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