Research Article Pharmacodynamics of TRPV1 Agonists in a Bioassay Using Human PC-3 Cells Daniel Alvarez-Berdugo, 1 Marcel Jiménez, 2,3 Pere Clavé, 1,2 and Laia Rofes 2 1 Laboratori de Fisiologia Digestiva, Departament de Cirurgia, Hospital de Matar´ o, Universitat Aut` onoma de Barcelona, 08304 Matar´ o, Spain 2 Centro de Investigaci´ on Biom´ edica en Red de Enfermedades Hep´ aticas y Digestivas, 28029 Madrid, Spain 3 Departament de Biologia Cel⋅lular, Fisiologia i Immunologia, Universitat Aut` onoma de Barcelona (UAB), 08193 Bellaterra, Spain Correspondence should be addressed to Pere Clav´ e; pere.clave@ciberehd.org Received 19 August 2013; Accepted 5 December 2013; Published 2 February 2014 Academic Editors: J.-T. Cheng and E. Hopper-Borge Copyright © 2014 Daniel Alvarez-Berdugo et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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 efect of the specifc 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 fuorescence following the addition of ionomycin. Concentration-response curves were ftted to the Hill equation. Results. Capsaicin and piperine had similar pharmacodynamics ( max 204.8 ± 184.3% piperine versus 176.6 ± 35.83% capsaicin,  = 0.8814, Hill coefcient 0.70 ± 0.50 piperine versus 1.59 ± 0.86 capsaicin,  = 0.3752). In contrast, capsaicinoids had lower  max (40.99 ± 6.14% capsaicinoids versus 176.6 ± 35.83% capsaicin,  < 0.001). All the TRPV1 agonists showed signifcant desensitization afer the second exposition and their efects were strongly inhibited by SB366791. Conclusion. TRPV1 receptor is successfully stimulated by capsaicin, piperine, and natural capsaicinoids. Tese agonists present desensitization and their efect is signifcantly reduced by a TRPV1-specifc antagonist. In addition, PC-3 cell bioassays proved useful in the study of TRPV1 pharmacodynamics. 1. Introduction Te transient receptor potential family V member 1 cation channel (TRPV1) is a nonselective channel that responds to noxious stimuli such as low pH, painful heat, and irritants. Identifcation of TRPV1 through molecular cloning such as the capsaicin receptor [1] represented a milestone in the study of noxious stimuli. Since then, many studies have tried to determine its druggability and pharmacological characteriza- tion [2–4]. TRPV1 is mainly expressed in unmyelinated C fbers and in A thinly myelinated fbers of the dorsal root (DRG), trigeminal ganglion (TG), and visceral aferent fbers and it plays an important role in temperature and pain perception. However, TRPV1 expression is not exclusive to neuronal tissue but can be found in other locations such as urothelial and epithelial cells [5, 6], which respond frst to irritating and infammatory stimuli together with aferent nociceptors [7, 8]. Upregulation of TRPV1 expression has been observed in various diseases [9] including those associated with visceral hypersensitivity such as irritable bowel syndrome [10] and other diseases like chronic cough [11] and neuropathic pain [12]. Downregulation of TRPV1 has been observed in some diseases such as periodontitis [13]. Strategies aiming to block or desensitize TRPV1 have been explored to treat several dis- eases such as neuropathic pain, spinal detrusor hyperrefexia, bladder hypersensitivity, and pruritus [3]. Hence, TRPV1 ago- nists and antagonists have become essential pharmacological tools to address the treatment of these disorders. Most bioassays aiming to characterize the pharmacody- namics of these TRPV1 ligands use human cells such as HEK293 heterologously expressing TRPV1 [14]. However, this technology is not available for most research groups Hindawi Publishing Corporation e Scientific World Journal Volume 2014, Article ID 184526, 6 pages http://dx.doi.org/10.1155/2014/184526