title: TRPM8 Channel Activation Induced by Monoterpenoid Rotundifolone Underlies Mesenteric Artery Relaxation.
abstract: In this study, our aims were to investigate transient receptor potential melastatin-8 channels (TRPM8) involvement in rotundifolone induced relaxation in the mesenteric artery and to increase the understanding of the role of these thermosensitive TRP channels in vascular tissue. Thus, message and protein levels of TRPM8 were measured by semi-quantitative PCR and western blotting in superior mesenteric arteries from 12 week-old Spague-Dawley (SD) rats. Isometric tension recordings evaluated the relaxant response in mesenteric rings were also performed. Additionally, the intracellular Ca2+ changes in mesenteric artery myocytes were measured using confocal microscopy. Using PCR and western blotting, both TRPM8 channel mRNA and protein expression was measured in SD rat mesenteric artery. Rotundifolone and menthol induced relaxation in the isolated superior mesenteric artery from SD rats and improved the relaxant response induced by cool temperatures. Also, this monoterpene induced an increase in transient intracellular Ca2+. These responses were significantly attenuated by pretreatment with capsazepine or BCTC, both TRPM8 channels blockers. The response induced by rotundifolone was not significantly attenuated by ruthenium red, a non-selective TRP channels blocker, or following capsaicin-mediated desensitization of TRPV1. Our findings suggest that rotundifolone induces relaxation by activating TRPM8 channels in rat superior mesenteric artery, more selectively than menthol, the classic TRPM8 agonist, and TRPM8 channels participates in vasodilatory pathways in isolated rat mesenteric arteries.
authors.affiliation: Departamento de Bio-regulação, Universidade Federal da Bahia (UFBA), Salvador, Bahia, Brazil, 40110-902.
authors.forename: Darizy Flavia
authors.initials: DF
authors.lastname: Silva
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba (UFPB), João Pessoa, Paraíba, Brazil, 58059-900.
authors.forename: Monica Moura
authors.initials: MM
authors.lastname: de Almeida
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba (UFPB), João Pessoa, Paraíba, Brazil, 58059-900.
authors.forename: Cinthia Guedes
authors.initials: CG
authors.lastname: Chaves
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba (UFPB), João Pessoa, Paraíba, Brazil, 58059-900.
authors.forename: Ana Letícia
authors.initials: AL
authors.lastname: Braz
authors.affiliation: Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil, 31270-901.
authors.forename: Maria Aparecida
authors.initials: MA
authors.lastname: Gomes
authors.affiliation: Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil, 31270-901.
authors.forename: Leidiane
authors.initials: L
authors.lastname: Pinho-da-Silva
authors.affiliation: Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil, 31270-901.
authors.forename: Jorge Luiz
authors.initials: JL
authors.lastname: Pesquero
authors.affiliation: Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil, 31270-901.
authors.forename: Viviane Aguiar
authors.initials: VA
authors.lastname: Andrade
authors.affiliation: Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil, 31270-901.
authors.forename: Maria de Fátima
authors.initials: Mde F
authors.lastname: Leite
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba (UFPB), João Pessoa, Paraíba, Brazil, 58059-900.
authors.forename: José George Ferreira
authors.initials: JG
authors.lastname: de Albuquerque
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba (UFPB), João Pessoa, Paraíba, Brazil, 58059-900.
authors.forename: Islania Giselia Albuquerque
authors.initials: IG
authors.lastname: Araujo
authors.affiliation: Núcleo de Estudos e Pesquisas de Plantas Medicinais da Universidade Federal do Vale do São Francisco, Petrolina, PE, Brasil, 56304-205.
authors.forename: Xirley Pereira
authors.initials: XP
authors.lastname: Nunes
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba (UFPB), João Pessoa, Paraíba, Brazil, 58059-900.
authors.forename: José Maria
authors.initials: JM
authors.lastname: Barbosa-Filho
authors.affiliation: Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil, 31270-901.
authors.forename: Jader dos Santos
authors.initials: Jdos S
authors.lastname: Cruz
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba (UFPB), João Pessoa, Paraíba, Brazil, 58059-900.
authors.forename: Nadja de Azevedo
authors.initials: Nde A
authors.lastname: Correia
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba (UFPB), João Pessoa, Paraíba, Brazil, 58059-900.
authors.forename: Isac Almeida
authors.initials: IA
authors.lastname: de Medeiros
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D003080:Cold Temperature; D003600:Cytosol / Q000378:metabolism; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects*; D008297:Male; D008610:Menthol / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D039821:Monoterpenes / Q000494:pharmacology*; D011719:Pyrazines / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012430:Ruthenium Red / Q000378:metabolism; D050053:TRPM Cation Channels / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D039821:Monoterpenes; C475772:N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamide; D011719:Pyrazines; D011725:Pyridines; D050053:TRPM Cation Channels; D050916:TRPV Cation Channels; C498947:Trpm8 protein, rat; C493922:Trpv1 protein, rat; D012430:Ruthenium Red; D008610:Menthol; C467828:rotundifolone; D002211:Capsaicin; D002118:Calcium