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dc.contributor.authorCastillo, Karen
dc.contributor.authorDuarte, Yorley
dc.contributor.authorSegura, Ignacio A.
dc.contributor.authorTricarico, Domenico
dc.contributor.authorChavez, Andres
dc.contributor.authorLatorre, Ramón
dc.contributor.authorMeza, Rodrigo
dc.contributor.authorAncaten, Carlos
dc.contributor.authorCarvajal-Zamorano, Karina
dc.contributor.authorScala, Rosa
dc.date.accessioned2023-03-15T12:49:44Z
dc.date.available2023-03-15T12:49:44Z
dc.date.issued2023
dc.identifier.urihttp://repositorio.ucm.cl/handle/ucm/4525
dc.description.abstractThe heat and capsaicin sensor, the transient receptor potential vanilloid type 1 (TRPV1) channel, is critically involved in pain sensation. Using compounds that activate TRPV1, such as capsaicin (CAP), produces analgesic effects. Hence the channel is a promising target for the management of pain conditions. However, when TRPV1 channels are sensitized in neuropathic pain conditions, inhibitors could be a better option for pain management. We have obtained evidence supporting that the bisphosphonate compound zoledronic acid (ZOL) acts as an inhibitor of the TRPV1 channel. ZOL is typically used in the treatment of bone diseases reducing bone mass loss, deterioration in bone microarchitecture and fracture risk, having as a collateral effect a decrease in pain sensation. We have observed, expressing TRPV1 in Xenopus laevis oocytes followed by patch-clamp recordings in inside-out configuration, that ZOL at doses ranging from 1 nM up to 30 μM reduces channel conductance and inhibits the activity of the channel deeply. Only high doses of CAP (≥ 10 μM) allow for recover of TRPV1 currents after ZOL treatment. Molecular modeling followed by docking analysis suggests that ZOL could potentially bind to TRPV1 at the vanilloid pocket and the PI(4,5)P2 binding site. Furthermore, like capsazepine, ZOL (100 nM) is able to eliminate the depression observed by applying CAP (1 μM) on synaptic transmission in the dentate gyrus. In addition, when ZOL is use during the induction of synaptic plasticity mediated by TRPV1, it eliminates plasticity. The compound did not affect the endocannabinoid production machinery suggesting that the ZOL is acting specifically on TRPV1 to hinder plasticity. Together, our evidence strongly supports that ZOL can inhibit TRPV1 activity.es_CL
dc.language.isoenes_CL
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 Chile*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/*
dc.sourceBiophysical Journal, 122(3 Supl. 1), 108aes_CL
dc.titleThe bisphosphonate zoledronic acid is a TRPV1 channel inhibitores_CL
dc.typeArticlees_CL
dc.ucm.indexacionScopuses_CL
dc.ucm.indexacionIsies_CL
dc.ucm.uricell.com/biophysj/fulltext/S0006-3495(22)01683-6#articleInformationes_CL
dc.ucm.doidoi.org/10.1016/j.bpj.2022.11.767es_CL


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