title: Inhibitory effect of positively charged triazine antagonists of prokineticin receptors on the transient receptor vanilloid type-1 (TRPV1) channel.
abstract: Four positively charged compounds, previously shown to produce analgesic activity by interacting with prokineticin receptor or T-type calcium channels, were tested for their ability to inhibit capsaicin-induced elevation of intracellular Ca(2+) in HEK-293 cells stably transfected with the human recombinant TRPV1, with the goal of identifying novel TRPV1 open-pore inhibitors. KYS-05090 showed the highest potency as a TRPV1 antagonist, even higher than that of the open-pore triazine inhibitor 8aA. The latter showed quite remarkable agonist/desensitizer activity at the rat recombinant TRPM8 channel. The activity of KYS-05090 and the other compounds was selective because none of these compounds was able to modulate the rat TRPA1 channel. Open-pore inhibitors of TRPV1 may be a new class of multi-target analgesics with lesser side effects, such as loss of acute pain sensitivity and hyperthermia, than most TRPV1 antagonists developed so far.
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, National Research Council, Via Campi Flegrei 34, Comprensorio Olivetti, 80078 Pozzuoli, Naples, Italy. Electronic address: luciano.depetrocellis@icb.cnr.it.
authors.forename: Luciano
authors.initials: L
authors.lastname: De Petrocellis
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, National Research Council, Via Campi Flegrei 34, Comprensorio Olivetti, 80078 Pozzuoli, Naples, Italy.
authors.forename: Aniello
authors.initials: A
authors.lastname: Schiano Moriello
authors.affiliation: Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Joon Seok
authors.initials: JS
authors.lastname: Byun
authors.affiliation: Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Joo Mi
authors.initials: JM
authors.lastname: Sohn
authors.affiliation: Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Jae Yeol
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Chemical and Biomolecular Nanotechnology and Department of Biological Chemistry and Molecular Modeling, Instituto de Quımica Avanzada de Cataluña (CSIC), Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Vázquez-Romero
authors.affiliation: Department of Chemical and Biomolecular Nanotechnology and Department of Biological Chemistry and Molecular Modeling, Instituto de Quımica Avanzada de Cataluña (CSIC), Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Garrido
authors.affiliation: Department of Chemical and Biomolecular Nanotechnology and Department of Biological Chemistry and Molecular Modeling, Instituto de Quımica Avanzada de Cataluña (CSIC), Barcelona, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Messeguer
authors.affiliation: Department of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary T2N 4N1, Canada.
authors.forename: Fang-Xiong
authors.initials: FX
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary T2N 4N1, Canada.
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Zamponi
authors.affiliation: Department of Life and Environmental Sciences, Unit of Pharmaceutical, Pharmacological and Nutraceutical Sciences, University of Cagliari, I-09124 Cagliari, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Deplano
authors.affiliation: Department of Life and Environmental Sciences, Unit of Pharmaceutical, Pharmacological and Nutraceutical Sciences, University of Cagliari, I-09124 Cagliari, Italy.
authors.forename: Cenzo
authors.initials: C
authors.lastname: Congiu
authors.affiliation: Department of Life and Environmental Sciences, Unit of Pharmaceutical, Pharmacological and Nutraceutical Sciences, University of Cagliari, I-09124 Cagliari, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Onnis
authors.affiliation: Department of Life and Environmental Sciences, Unit of Pharmaceutical, Pharmacological and Nutraceutical Sciences, University of Cagliari, I-09124 Cagliari, Italy. Electronic address: gbalboni@unica.it.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Balboni
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, National Research Council, Via Campi Flegrei 34, Comprensorio Olivetti, 80078 Pozzuoli, Naples, Italy. Electronic address: vdimarzo@icb.cnr.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000378:metabolism; D002460:Cell Line; D005334:Fever / Q000188:drug therapy / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D010146:Pain / Q000188:drug therapy / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D018000:Receptors, Peptide / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism*; D014227:Triazines / Q000494:pharmacology*
chemical_list: D000700:Analgesics; C549128:KYS 05090; D011799:Quinazolines; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D050916:TRPV Cation Channels; D014227:Triazines; D002211:Capsaicin; D002118:Calcium
keywords: Calcium channel assay; Open-pore inhibitors; Prokineticin receptors; TRPM8 receptor; TRPV1 receptor