title: Pharmacodynamics of TRPV1 agonists in a bioassay using human PC-3 cells.
abstract: OBJECTIVE
  TRPV1 is a multimodal channel mainly expressed in sensory neurons. We aimed to explore the pharmacodynamics of the TRPV1 agonists, capsaicin, natural capsaicinoids, and piperine in an in vitro bioassay using human PC-3 cells and to examine desensitization and the effect of the specific antagonist SB366791.
  
  
  METHODS
  PC-3 cells expressing TRPV1 were incubated with Fluo-4. Fluorescence emission changes following exposition to agonists with and without preincubation with antagonists were assessed and referred to maximal fluorescence following the addition of ionomycin. Concentration-response curves were fitted to the Hill equation.
  
  
  RESULTS
  Capsaicin and piperine had similar pharmacodynamics (E max 204.8 ± 184.3% piperine versus 176.6 ± 35.83% capsaicin, P = 0.8814, Hill coefficient 0.70 ± 0.50 piperine versus 1.59 ± 0.86 capsaicin, P = 0.3752). In contrast, capsaicinoids had lower E max (40.99 ± 6.14% capsaicinoids versus 176.6 ± 35.83% capsaicin, P < 0.001). All the TRPV1 agonists showed significant desensitization after the second exposition and their effects were strongly inhibited by SB366791.
  
  
  CONCLUSIONS
  TRPV1 receptor is successfully stimulated by capsaicin, piperine, and natural capsaicinoids. These agonists present desensitization and their effect is significantly reduced by a TRPV1-specific antagonist. In addition, PC-3 cell bioassays proved useful in the study of TRPV1 pharmacodynamics.
authors.affiliation: Laboratori de Fisiologia Digestiva, Departament de Cirurgia, Hospital de Mataró, Universitat Autònoma de Barcelona, 08304 Mataró, Spain.
authors.forename: Daniel
authors.identifier: 0000-0003-0338-0793
authors.initials: D
authors.lastname: Alvarez-Berdugo
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, 28029 Madrid, Spain ; Departament de Biologia Cel · lular, Fisiologia i Immunologia, Universitat Autònoma de Barcelona (UAB), 08193 Bellaterra, Spain.
authors.forename: Marcel
authors.initials: M
authors.lastname: Jiménez
authors.affiliation: Laboratori de Fisiologia Digestiva, Departament de Cirurgia, Hospital de Mataró, Universitat Autònoma de Barcelona, 08304 Mataró, Spain ; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, 28029 Madrid, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Clavé
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, 28029 Madrid, Spain.
authors.forename: Laia
authors.identifier: 0000-0002-1628-5253
authors.initials: L
authors.lastname: Rofes
mesh_terms: D000470:Alkaloids / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D017209:Apoptosis / Q000187:drug effects; D052117:Benzodioxoles / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001681:Biological Assay / Q000379:methods; D002211:Capsaicin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D010880:Piperidines / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D050916:TRPV Cation Channels / Q000819:agonists*
chemical_list: D000470:Alkaloids; D052117:Benzodioxoles; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D002211:Capsaicin; C008922:piperine