dc.creator | Dhuna, K. | es |
dc.creator | Felgate, M. | es |
dc.creator | Bidula, S.M. | es |
dc.creator | Walpole, Samuel | es |
dc.creator | Bibic, L. | es |
dc.creator | Cromer, B.A. | es |
dc.creator | Angulo Álvarez, Jesús | es |
dc.creator | Sanderson, J. | es |
dc.creator | Stebbing, M.J. | es |
dc.creator | Stokes, L. | es |
dc.date.accessioned | 2020-06-09T11:03:38Z | |
dc.date.available | 2020-06-09T11:03:38Z | |
dc.date.issued | 2019 | |
dc.identifier.citation | Dhuna, K., Felgate, M., Bidula, S.M., Walpole, S., Bibic, L., Cromer, B.A.,...,Stokes, L. (2019). Ginsenosides act as positive modulators of P2X4 receptors. Molecular Pharmacology, 95 (2), 210-221. | |
dc.identifier.issn | 0026-895X (impreso) | es |
dc.identifier.issn | 1521-0111 (electrónico) | es |
dc.identifier.uri | https://hdl.handle.net/11441/97595 | |
dc.description.abstract | We investigated the selectivity of protopanaxadiol ginsenosides from Panax ginseng acting as positive allosteric modulators on P2X receptors. ATP-induced responses were measured in stable cell lines overexpressing human P2X4 using a YOPRO-1 dye uptake assay, intracellular calcium measurements, and whole-cell patch-clamp recordings. Ginsenosides CK and Rd were demonstrated to enhance ATP responses at P2X4 by ∼twofold, similar to potentiation by the known positive modulator ivermectin. Investigations into the role of P2X4 in mediating a cytotoxic effect showed that only P2X7 expression in HEK-293 cells induces cell death in response to high concentrations of ATP, and that ginsenosides can enhance this process. Generation of a P2X7-deficient clone of BV-2 microglial cells using CRISPR/ Cas9 gene editing enabled an investigation of endogenous P2X4 in a microglial cell line. Compared with parental BV-2 cells, P2X7-deficient BV-2 cells showed minor potentiation of ATP responses by ginsenosides, and insensitivity to ATP 2 or ATP 1 ginsenoside-induced cell death, indicating a primary role for P2X7 receptors in both of these effects. Computational docking to a homology model of human P2X4, based on the open state of zfP2X4, yielded evidence of a putative ginsenoside binding site in P2X4 in the central vestibule region of the large ectodomain. | es |
dc.format | application/pdf | es |
dc.format.extent | 12 p. | es |
dc.language.iso | eng | es |
dc.publisher | American Society for Pharmacology and Experimental Therapeutics (ASPET) | es |
dc.relation.ispartof | Molecular Pharmacology, 95 (2), 210-221. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.title | Ginsenosides act as positive modulators of P2X4 receptors | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Química orgánica | es |
dc.relation.publisherversion | https://doi.org/10.1124/mol.118.113696 | es |
dc.identifier.doi | 10.1124/mol.118.113696 | es |
dc.journaltitle | Molecular Pharmacology | es |
dc.publication.volumen | 95 | es |
dc.publication.issue | 2 | es |
dc.publication.initialPage | 210 | es |
dc.publication.endPage | 221 | es |