title: Competitive inhibition of TRPV1-calmodulin interaction by vanilloids.
abstract: There is enormous interest toward vanilloid agonists of the pain receptor TRPV1 in analgesic therapy, but the mechanisms of their sensory neuron-blocking effects at high or repeated doses are still a matter of debate. Our results have demonstrated that capsaicin and resiniferatoxin form nanomolar complexes with calmodulin, and competitively inhibit TRPV1-calmodulin interaction. These interactions involve the protein recognition interface of calmodulin, which is responsible for all of the cell-regulatory calmodulin-protein interactions. These results draw attention to a previously unknown vanilloid target, which may contribute to the explanation of the paradoxical pain-modulating behavior of these important pharmacons.
authors.affiliation: Department of Medical Chemistry, University of Szeged, Hungary.
authors.forename: Anasztázia
authors.initials: A
authors.lastname: Hetényi
authors.affiliation: SZTE-MTA Lendület Foldamer Research Group, Institute of Pharmaceutical Analysis, University of Szeged, Hungary.
authors.forename: Lukács
authors.initials: L
authors.lastname: Németh
authors.affiliation: SZTE-MTA Lendület Foldamer Research Group, Institute of Pharmaceutical Analysis, University of Szeged, Hungary.
authors.forename: Edit
authors.initials: E
authors.lastname: Wéber
authors.affiliation: Institute of Pharmaceutical Analysis, University of Szeged, Hungary.
authors.forename: Gerda
authors.initials: G
authors.lastname: Szakonyi
authors.affiliation: Institute of Pharmaceutical Analysis, University of Szeged, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Winter
authors.affiliation: Institute of Pharmaceutical Analysis, University of Szeged, Hungary.|Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Jósvay
authors.affiliation: SZTE-MTA Lendület Foldamer Research Group, Institute of Pharmaceutical Analysis, University of Szeged, Hungary.
authors.forename: Éva
authors.initials: É
authors.lastname: Bartus
authors.affiliation: Institute of Pharmaceutical Analysis, University of Szeged, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Oláh
authors.affiliation: SZTE-MTA Lendület Foldamer Research Group, Institute of Pharmaceutical Analysis, University of Szeged, Hungary.|Institute of Pharmaceutical Analysis, University of Szeged, Hungary.
authors.forename: Tamás A
authors.initials: TA
authors.lastname: Martinek
mesh_terms: D001665:Binding Sites; D002147:Calmodulin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002211:Capsaicin / Q000378:metabolism / Q000494:pharmacology; D004224:Diterpenes / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D010146:Pain / Q000188:drug therapy / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D060066:Protein Interaction Maps / Q000187:drug effects* / Q000235:genetics; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D002147:Calmodulin; D004224:Diterpenes; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; C024353:resiniferatoxin; D002211:Capsaicin
keywords: TRPV1; calmodulin; capsaicin; resiniferatoxin; vanilloid