| Author | Alves, Quiara Lovatti | |
| Author | Moraes, Raiana dos Anjos | |
| Author | Froes, Thamires Quadros | |
| Author | Castilho, Marcelo Santos | |
| Author | Araújo, Rodrigo Santos Aquino de | |
| Author | Barbosa Filho, José Maria | |
| Author | Meira, Cássio Santana | |
| Author | Soares, Milena Botelho Pereira | |
| Author | Silva, Darízy Flávia | |
| Access date | 2021-01-07T13:38:15Z | |
| Available date | 2021-01-07T13:38:15Z | |
| Document date | 2020 | |
| Citation | ALVES, 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. 1-14, Nov. 2020. | pt_BR |
| ISSN | 0014-2999 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/45523 | |
| Sponsorship | National 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. | pt_BR |
| Language | eng | pt_BR |
| Publisher | Elsevier | pt_BR |
| Rights | open access | pt_BR |
| Subject in Portuguese | 7-Hidroxicumarina | pt_BR |
| Subject in Portuguese | Vasodilatação | pt_BR |
| Subject in Portuguese | Canais de potássio | pt_BR |
| Subject in Portuguese | Sistema Cardiovascular | pt_BR |
| Title | Inhibition of intracellular Ca2+ mobilization and potassium channels activation are involved in the vasorelaxation induced by 7-hydroxycoumarin | pt_BR |
| Type | Article | pt_BR |
| DOI | 10.1016/j.ejphar.2020.173525 | |
| Abstract | Coumarins 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. | pt_BR |
| Affilliation | Federal University of Bahia. Laboratory of Cardiovascular Physiology and Pharmacology. Salvador, BA, Brazil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
| Affilliation | Federal University of Bahia. Laboratory of Cardiovascular Physiology and Pharmacology. Salvador, BA, Brazil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
| Affilliation | Federal University of Bahia. Faculty of Pharmacy. Laboratory of Bioinformatics and Molecular Modeling. Salvador, BA, Brazil. | pt_BR |
| Affilliation | Federal University of Bahia. Faculty of Pharmacy. Laboratory of Bioinformatics and Molecular Modeling. Salvador, BA, Brazil. | pt_BR |
| Affilliation | Federal University of Paraíba. Laboratory of Pharmaceutical Technology, Department of Physiology and Pathology. João Pessoa, PB, Brazil. | pt_BR |
| Affilliation | Federal University of Paraíba. Laboratory of Pharmaceutical Technology, Department of Physiology and Pathology. João Pessoa, PB, Brazil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
| Affilliation | Federal University of Bahia. Laboratory of Cardiovascular Physiology and Pharmacology. Salvador, BA, Brazil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
| Subject | 7-Hydroxycoumarin | pt_BR |
| Subject | Vasorelaxation | pt_BR |
| Subject | K+ channels | pt_BR |
| Subject | FTMap | pt_BR |
| Subject | Docking | pt_BR |
| Subject | Cardiovascular System | pt_BR |
