title: Pharmacological characterisation of the plant sesquiterpenes polygodial and drimanial as vanilloid receptor agonists.
abstract: This study was designed to assess the participation of transient receptor potential vanilloid 1 (TRPV1) in the biological effects induced by the plant-derived sesquiterpenes polygodial and drimanial. In rat isolated urinary bladder, polygodial and drimanial produced a tachykinin-mediated contraction that was inhibited by combination of NK(1) and NK(2) tachykinin receptor antagonists, SR 140333 and SR 48968. Furthermore, two different TRPV1 antagonists, capsazepine and ruthenium red prevented the contraction induced by both compounds. In addition, capsaicin, polygodial and drimanial displaced in a concentration-dependent manner the specific binding sites of [(3)H]-resiniferatoxin to rat spinal cord membranes, with a IC(50) values of 0.48, 4.2 and 3.2 microM, respectively. Likewise, capsaicin, polygodial and drimanial promoted an increase of [(45)Ca(2+)] uptake in rat spinal cord synaptosomes. In cultured rat trigeminal neurons, polygodial, drimanial and capsaicin were also able to significantly increase the intracellular Ca(2+) levels, effect that was significantly prevented by capsazepine. Together, the present results strongly suggest that the pharmacological actions of plant-derived sesquiterpenes polygodial and drimanial, seem to be partially mediated by activation of TRPV1. Additional investigations are needed to completely define the pharmacodynamic properties of these sesquiterpenes.
authors.affiliation: Department of Pharmacology, Federal University of Santa Catarina, CCB, Campus Universitário Trindade, Florianópolis, Brazil.
authors.forename: Eunice
authors.initials: E
authors.lastname: André
authors.forename: Barbara
authors.initials: B
authors.lastname: Campi
authors.forename: Marcello
authors.initials: M
authors.lastname: Trevisani
authors.forename: Juliano
authors.initials: J
authors.lastname: Ferreira
authors.forename: Angela
authors.initials: A
authors.lastname: Malheiros
authors.forename: Rosendo A
authors.initials: RA
authors.lastname: Yunes
authors.forename: João B
authors.initials: JB
authors.lastname: Calixto
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Geppetti
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D024301:Plant Bark / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D050916:TRPV Cation Channels / Q000819:agonists*; D012668:Trigeminal Ganglion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism; D032423:Winteraceae / Q000737:chemistry*
chemical_list: D012717:Sesquiterpenes; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C469416:drimanial; C034380:polygodial; D002118:Calcium