Arginine-rich peptides are blockers of VR-1 channels with analgesic activity

Vanilloid receptors (VRs) play a fundamental role in the transduction of peripheral tissue injury and/or inflammation responses. Molecules that antagonize VR channel activity may act as selective and potent analgesics. We report that synthetic arginine-rich hexapeptides block heterologously expresse...

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Authors: Planells-Cases, Rosa, Aracil-Marco, Adolfo, Merino, Jaime M., Gallar, Juana, Pérez-Payâ, Enrique, Belmonte, Carlos, González Ros, José Manuel, Ferrer-Montiel, Antonio
Format: article
Status:Published version
Publication Date:2000
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/288703
Online Access:http://hdl.handle.net/10261/288703
Access Level:Open access
Keyword:Pain
Nociceptor
Capsaicin
Dynorphin
Non-competitive antagonist
Ionic pore
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network_acronym_str ES
network_name_str España
repository_id_str
spelling Arginine-rich peptides are blockers of VR-1 channels with analgesic activityPlanells-Cases, RosaAracil-Marco, AdolfoMerino, Jaime M.Gallar, JuanaPérez-Payâ, EnriqueBelmonte, CarlosGonzález Ros, José ManuelFerrer-Montiel, AntonioPainNociceptorCapsaicinDynorphinNon-competitive antagonistIonic poreVanilloid receptors (VRs) play a fundamental role in the transduction of peripheral tissue injury and/or inflammation responses. Molecules that antagonize VR channel activity may act as selective and potent analgesics. We report that synthetic arginine-rich hexapeptides block heterologously expressed VR-1 channels with submicromolar efficacy in a weak voltage-dependent manner, consistent with a binding site located near/at the entryway of the aqueous pore. Dynorphins, natural arginine-rich peptides, also blocked VR-1 activity with micromolar affinity. Notably, synthetic and natural arginine-rich peptides attenuated the ocular irritation produced by topical capsaicin application onto the eyes of experimental animals. Taken together, our results imply that arginine-rich peptides are VR-1 channel blockers with analgesic activity. These findings may expand the development of novel analgesics by targeting receptor sites distinct from the capsaicin binding site.This work was supported by grants from La Fundación La Caixa (98/027-00 to A.F.M.), the Spanish Interministerial Commission of Science and Technology (CICYT) and the European Commission (FEDER) (1FD97-0662-C02-01 and 02, to A.F.M. and E.P.P.), and the CICYT (SAF99-0066-C02-01 and 02, to C.B. and J.G.).Peer reviewedElsevierFundación la CaixaEuropean CommissionComisión Interministerial de Ciencia y Tecnología, CICYT (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202320232000info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/288703reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésFEBS Lettershttps://doi.org/10.1016/S0014-5793(00)01982-7Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2887032026-05-22T06:33:51Z
dc.title.none.fl_str_mv Arginine-rich peptides are blockers of VR-1 channels with analgesic activity
title Arginine-rich peptides are blockers of VR-1 channels with analgesic activity
spellingShingle Arginine-rich peptides are blockers of VR-1 channels with analgesic activity
Planells-Cases, Rosa
Pain
Nociceptor
Capsaicin
Dynorphin
Non-competitive antagonist
Ionic pore
title_short Arginine-rich peptides are blockers of VR-1 channels with analgesic activity
title_full Arginine-rich peptides are blockers of VR-1 channels with analgesic activity
title_fullStr Arginine-rich peptides are blockers of VR-1 channels with analgesic activity
title_full_unstemmed Arginine-rich peptides are blockers of VR-1 channels with analgesic activity
title_sort Arginine-rich peptides are blockers of VR-1 channels with analgesic activity
dc.creator.none.fl_str_mv Planells-Cases, Rosa
Aracil-Marco, Adolfo
Merino, Jaime M.
Gallar, Juana
Pérez-Payâ, Enrique
Belmonte, Carlos
González Ros, José Manuel
Ferrer-Montiel, Antonio
author Planells-Cases, Rosa
author_facet Planells-Cases, Rosa
Aracil-Marco, Adolfo
Merino, Jaime M.
Gallar, Juana
Pérez-Payâ, Enrique
Belmonte, Carlos
González Ros, José Manuel
Ferrer-Montiel, Antonio
author_role author
author2 Aracil-Marco, Adolfo
Merino, Jaime M.
Gallar, Juana
Pérez-Payâ, Enrique
Belmonte, Carlos
González Ros, José Manuel
Ferrer-Montiel, Antonio
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Fundación la Caixa
European Commission
Comisión Interministerial de Ciencia y Tecnología, CICYT (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Pain
Nociceptor
Capsaicin
Dynorphin
Non-competitive antagonist
Ionic pore
topic Pain
Nociceptor
Capsaicin
Dynorphin
Non-competitive antagonist
Ionic pore
description Vanilloid receptors (VRs) play a fundamental role in the transduction of peripheral tissue injury and/or inflammation responses. Molecules that antagonize VR channel activity may act as selective and potent analgesics. We report that synthetic arginine-rich hexapeptides block heterologously expressed VR-1 channels with submicromolar efficacy in a weak voltage-dependent manner, consistent with a binding site located near/at the entryway of the aqueous pore. Dynorphins, natural arginine-rich peptides, also blocked VR-1 activity with micromolar affinity. Notably, synthetic and natural arginine-rich peptides attenuated the ocular irritation produced by topical capsaicin application onto the eyes of experimental animals. Taken together, our results imply that arginine-rich peptides are VR-1 channel blockers with analgesic activity. These findings may expand the development of novel analgesics by targeting receptor sites distinct from the capsaicin binding site.
publishDate 2000
dc.date.none.fl_str_mv 2000
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/288703
url http://hdl.handle.net/10261/288703
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv FEBS Letters
https://doi.org/10.1016/S0014-5793(00)01982-7
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869422826811817984
score 15,198674

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