Pharmacodynamics of TRPV1 Agonists in a Bioassay Using Human PC-3 Cells
Alvarez Berdugo, Daniel (Universitat Autònoma de Barcelona)
Jiménez Farrerons, Marcel (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Clavé i Civit, Pere (Universitat Autònoma de Barcelona)
Rofes, Laia (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas)

Data:	2014
Resum:	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 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 (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.
Ajuts:	Ministerio de Ciencia e Innovación PS09-01012 Ministerio de Ciencia e Innovación INT-10-228 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-708 Agència de Gestió d'Ajuts Universitaris i de Recerca 2011/CTP-00032
Nota:	Altres ajuts: La Fundació Marató de TV3
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	The Scientific World Journal, Vol. 2014 (February 2014) , art. 184526, ISSN 1537-744X

DOI: 10.1155/2014/184526
PMID: 24688365

6 p, 1.0 MB

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