Pharmacodynamics of TRPV1 Agonists in a Bioassay Using Human PC-3 Cells. (2nd February 2014)

• Record Type: Journal Article
• Authors: Alvarez-Berdugo, Daniel; Jiménez, Marcel; Clavé, Pere; Rofes, Laia
• Other Names: Cheng J.-T. Academic Editor.; Hopper-Borge E. Academic Editor.
• Is Part Of: TheScientificWorldjournal. Volume 2014(2014)
• Publication Date: 2014-02-02
• Subjects: Science -- Periodicals; Technology -- Periodicals; Medicine -- Periodicals; 505
• DOI: 10.1155/2014/184526
• Languages: English
• ISSNs: 2356-6140

Abstract

Abstract : Purpose . 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. Conclusion . 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.