Pharmacodynamics of TRPV1 Agonists in a Bioassay Using Human PC-3 Cells
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 anta...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | The Scientific World Journal |
| Online Access: | http://dx.doi.org/10.1155/2014/184526 |
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| author | Daniel Alvarez-Berdugo Marcel Jiménez Pere Clavé Laia Rofes |
| author_facet | Daniel Alvarez-Berdugo Marcel Jiménez Pere Clavé Laia Rofes |
| author_sort | Daniel Alvarez-Berdugo |
| collection | DOAJ |
| description | 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 (Emax 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 Emax (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. |
| format | Article |
| id | doaj-art-9de868c73ab647d787b2bc2c991b1ca3 |
| institution | Kabale University |
| issn | 2356-6140 1537-744X |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Scientific World Journal |
| spelling | doaj-art-9de868c73ab647d787b2bc2c991b1ca32025-02-03T06:07:21ZengWileyThe Scientific World Journal2356-61401537-744X2014-01-01201410.1155/2014/184526184526Pharmacodynamics of TRPV1 Agonists in a Bioassay Using Human PC-3 CellsDaniel Alvarez-Berdugo0Marcel Jiménez1Pere Clavé2Laia Rofes3Laboratori de Fisiologia Digestiva, Departament de Cirurgia, Hospital de Mataró, Universitat Autònoma de Barcelona, 08304 Mataró, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, 28029 Madrid, SpainLaboratori de Fisiologia Digestiva, Departament de Cirurgia, Hospital de Mataró, Universitat Autònoma de Barcelona, 08304 Mataró, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, 28029 Madrid, SpainPurpose. 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 (Emax 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 Emax (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.http://dx.doi.org/10.1155/2014/184526 |
| spellingShingle | Daniel Alvarez-Berdugo Marcel Jiménez Pere Clavé Laia Rofes Pharmacodynamics of TRPV1 Agonists in a Bioassay Using Human PC-3 Cells The Scientific World Journal |
| title | Pharmacodynamics of TRPV1 Agonists in a Bioassay Using Human PC-3 Cells |
| title_full | Pharmacodynamics of TRPV1 Agonists in a Bioassay Using Human PC-3 Cells |
| title_fullStr | Pharmacodynamics of TRPV1 Agonists in a Bioassay Using Human PC-3 Cells |
| title_full_unstemmed | Pharmacodynamics of TRPV1 Agonists in a Bioassay Using Human PC-3 Cells |
| title_short | Pharmacodynamics of TRPV1 Agonists in a Bioassay Using Human PC-3 Cells |
| title_sort | pharmacodynamics of trpv1 agonists in a bioassay using human pc 3 cells |
| url | http://dx.doi.org/10.1155/2014/184526 |
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