Inhibition of intracellular Ca2+ mobilization and potassium channels activation are involved in the vasorelaxation induced by 7-hydroxycoumarin

dc.creatorAlves, Quiara Lovatti
dc.creatorMoraes, Raiana dos Anjos
dc.creatorFroes, Thamires Quadros
dc.creatorCastilho, Marcelo Santos
dc.creatorAraújo, Rodrigo Santos Aquino de
dc.creatorBarbosa Filho, José Maria
dc.creatorMeira, Cássio Santana
dc.creatorSoares, Milena Botelho Pereira
dc.creatorSilva, Darízy Flávia
dc.date2020-11-30T12:18:34Z
dc.date2020-11-30T12:18:34Z
dc.date2020
dc.date.accessioned2023-09-26T20:07:28Z
dc.date.available2023-09-26T20:07:28Z
dc.identifierALVES, Quiara Lovatti et al. Inhibition of intracellular Ca2+ mobilization and potassium channels activation are involved in the vasorelaxation induced by 7-hydroxycoumarin. European Journal of Pharmacology, v. 887, p. 173525, 2020.
dc.identifier0014-2999
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/44667
dc.identifier10.1016/j.ejphar.2020.173525
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8849065
dc.descriptionNational Council for Scientific and Technological Development (CNPq) 306106/2017–5 and Coordination for the Improvement of Higher Education Personnel (CAPES) - Finance Code 001. We acknowledge the computational support from SCC1 (Boston University) and technical support from Pedro S. Lacerda.
dc.descriptionCoumarins exhibit a wide variety of biological effects, including activities in the cardiovascular system and the aim of this study was to evaluate the vascular therapeutic potential of 7-Hydroxicoumarin (7-HC). The vascular effects induced by 7-HC (0.001 μM–300 μM), were investigated by in vitro approaches using isometric tension measurements in rat superior mesenteric arteries and by in silico assays using Ligand-based analysis. Our results suggest that the vasorelaxant effect of 7-HC seems to rely on potassium channels, notably through large conductance Ca2+-activated K+ (BKCa) channels activation. In fact, 7-HC (300 μM) significantly reduced CaCl2- induced contraction as well as the reduction of intracellular calcium mobilization. However, the relaxation induced by 7-HC was independent of store-operated calcium entry (SOCE). Moreover, in silico analysis suggests that potassium channels have a common binding pocket, where 7-HC may bind and hint that its binding profile is more similar to quinine’s than verapamil’s. These results are compatible with the inhibition of Ca2+ release from intracellular stores, which is prompted by phenylephrine and caffeine. Taken together, these results demonstrate a therapeutic potential of 7-HC on the cardiovascular system, making it a promising lead compound for the development of drugs useful in the treatment of cardiovascular diseases.
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier
dc.rightsopen access
dc.subjectCumarinas
dc.subjectVasorrelaxamento
dc.subjectCanais K
dc.subjectDoenças cardiovasculares.
dc.subject7-Hydroxycoumarin
dc.subjectVasorelaxation
dc.subjectK+ channels
dc.subjectFTMap
dc.subjectDocking
dc.titleInhibition of intracellular Ca2+ mobilization and potassium channels activation are involved in the vasorelaxation induced by 7-hydroxycoumarin
dc.typeArticle


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