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dc.contributor.authorDhuna, K
dc.contributor.authorFelgate, M
dc.contributor.authorBidula, SM
dc.contributor.authorWalpole, S
dc.contributor.authorBibic, L
dc.contributor.authorCromer, BA
dc.contributor.authorAngulo, J
dc.contributor.authorSanderson, J
dc.contributor.authorStebbing, MJ
dc.contributor.authorStokes, L
dc.date.accessioned2020-12-10T00:59:06Z
dc.date.available2020-12-10T00:59:06Z
dc.date.issued2019-02-01
dc.identifierpii: mol.118.113696
dc.identifier.citationDhuna, K., Felgate, M., Bidula, S. M., Walpole, S., Bibic, L., Cromer, B. A., Angulo, J., Sanderson, J., Stebbing, M. J. & Stokes, L. (2019). Ginsenosides Act As Positive Modulators of P2X4 Receptors. MOLECULAR PHARMACOLOGY, 95 (2), pp.210-221. https://doi.org/10.1124/mol.118.113696.
dc.identifier.issn0026-895X
dc.identifier.urihttp://hdl.handle.net/11343/253628
dc.description.abstractWe 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- or ATP+ 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.
dc.languageEnglish
dc.publisherAMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleGinsenosides Act As Positive Modulators of P2X4 Receptors
dc.typeJournal Article
dc.identifier.doi10.1124/mol.118.113696
melbourne.affiliation.departmentAnatomy and Neuroscience
melbourne.source.titleMolecular Pharmacology
melbourne.source.volume95
melbourne.source.issue2
melbourne.source.pages210-221
dc.rights.licenseCC BY
melbourne.elementsid1362957
melbourne.contributor.authorStebbing, Martin
dc.identifier.eissn1521-0111
melbourne.accessrightsOpen Access


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