Characterization of an anandamide degradation system in prostate epithelial PC-3 cells:synthesis of new transporter inhibitors as tools for this study

11 p.

Detalles Bibliográficos
Autores: Ruiz Llorente, Lidia|||0000-0003-1430-9618, Ortega Gutiérrez, Silvia, Viso, Alma, Sánchez Alonso, María de Gracia, Sánchez García, Ana María, Fernández, Carlos, Ramos, José A., Hillard, Cecilia, Lasunción Ripa, Miguel A, López Rodríguez, María L., Díaz-Laviada Marturet, Inés Cecilia|||0000-0001-9704-4373
Tipo de recurso: artículo
Fecha de publicación:2004
País:España
Institución:Universidad de Alcalá (UAH)
Repositorio:e_Buah Biblioteca Digital Universidad de Alcalá
Idioma:inglés
OAI Identifier:oai:ebuah.uah.es:10017/62380
Acceso en línea:http://hdl.handle.net/10017/62380
https://dx.doi.org/10.1038/sj.bjp.0705628
Access Level:acceso abierto
Palabra clave:Anandamide degradation
Anandamide uptake inhibitors
Prostate PC-3 cells
Fatty acid amidohydrolase
Endogenous cannabinoid system
Biología y Biomedicina/Biología
Biology
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spelling Characterization of an anandamide degradation system in prostate epithelial PC-3 cells:synthesis of new transporter inhibitors as tools for this studyRuiz Llorente, Lidia|||0000-0003-1430-9618Ortega Gutiérrez, SilviaViso, AlmaSánchez Alonso, María de GraciaSánchez García, Ana MaríaFernández, CarlosRamos, José A.Hillard, CeciliaLasunción Ripa, Miguel ALópez Rodríguez, María L.Díaz-Laviada Marturet, Inés Cecilia|||0000-0001-9704-4373Anandamide degradationAnandamide uptake inhibitorsProstate PC-3 cellsFatty acid amidohydrolaseEndogenous cannabinoid systemBiología y Biomedicina/BiologíaBiology11 p.The response of anandamide is terminated by a carrier-mediated transport followed by degradation catalyzed by the cloned enzyme fatty acid amidohydrolase (FAAH). In this study, we provide biochemical data showing an anandamide uptake process and the expression of FAAH in human prostate. Anandamide was accumulated in PC-3 cells by a saturable and temperature-dependent process. Kinetic studies of anandamide uptake, determined in the presence of cannabinoid and vanilloid antagonists, revealed apparent parameters of KM=4.7+/-0.2 microm and Vmax=3.3+/-0.3 pmol min-1 (10(6) cells)-1. The accumulation of anandamide was moderately inhibited by previously characterized anandamide transporter inhibitors (AM404, UCM707 and VDM11) but was unaffected by inhibitors of other lipid transport systems (phloretin or verapamil) and moderately affected by the FAAH inhibitor methyl arachidonyl fluorophosphonate. The presence of FAAH in human prostate epithelial PC-3 cells was confirmed by analyzing its expression by Western blot and measuring FAAH activity. To further study the structural requirements of the putative carrier, we synthesized a series of structurally different compounds 1-8 and evaluated their capacity as uptake inhibitors. They showed different inhibitory capacity in PC-3 cells, with (9Z,12Z)-N-(fur-3-ylmethyl)octadeca-9,12-dienamide (4, UCM119) being the most efficacious, with maximal inhibition and IC50 values of 49% and 11.3+/-0.5 microM, respectively. In conclusion, PC-3 cells possess a complete inactivation system for anandamide formed by an uptake process and the enzyme FAAH. These results suggest a possible physiological function of anandamide in the prostate, reinforcing the role of endocannabinoid system as a neuroendocrine modulator.Ministerio de Ciencia y TecnologíaAgencia Antidroga de la Comunidad de Madrid20042004-03-01journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10017/62380https://dx.doi.org/10.1038/sj.bjp.0705628reponame:e_Buah Biblioteca Digital Universidad de Alcaláinstname:Universidad de Alcalá (UAH)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ebuah.uah.es:10017/623802026-06-18T11:13:07Z
dc.title.none.fl_str_mv Characterization of an anandamide degradation system in prostate epithelial PC-3 cells:synthesis of new transporter inhibitors as tools for this study
title Characterization of an anandamide degradation system in prostate epithelial PC-3 cells:synthesis of new transporter inhibitors as tools for this study
spellingShingle Characterization of an anandamide degradation system in prostate epithelial PC-3 cells:synthesis of new transporter inhibitors as tools for this study
Ruiz Llorente, Lidia|||0000-0003-1430-9618
Anandamide degradation
Anandamide uptake inhibitors
Prostate PC-3 cells
Fatty acid amidohydrolase
Endogenous cannabinoid system
Biología y Biomedicina/Biología
Biology
title_short Characterization of an anandamide degradation system in prostate epithelial PC-3 cells:synthesis of new transporter inhibitors as tools for this study
title_full Characterization of an anandamide degradation system in prostate epithelial PC-3 cells:synthesis of new transporter inhibitors as tools for this study
title_fullStr Characterization of an anandamide degradation system in prostate epithelial PC-3 cells:synthesis of new transporter inhibitors as tools for this study
title_full_unstemmed Characterization of an anandamide degradation system in prostate epithelial PC-3 cells:synthesis of new transporter inhibitors as tools for this study
title_sort Characterization of an anandamide degradation system in prostate epithelial PC-3 cells:synthesis of new transporter inhibitors as tools for this study
dc.creator.none.fl_str_mv Ruiz Llorente, Lidia|||0000-0003-1430-9618
Ortega Gutiérrez, Silvia
Viso, Alma
Sánchez Alonso, María de Gracia
Sánchez García, Ana María
Fernández, Carlos
Ramos, José A.
Hillard, Cecilia
Lasunción Ripa, Miguel A
López Rodríguez, María L.
Díaz-Laviada Marturet, Inés Cecilia|||0000-0001-9704-4373
author Ruiz Llorente, Lidia|||0000-0003-1430-9618
author_facet Ruiz Llorente, Lidia|||0000-0003-1430-9618
Ortega Gutiérrez, Silvia
Viso, Alma
Sánchez Alonso, María de Gracia
Sánchez García, Ana María
Fernández, Carlos
Ramos, José A.
Hillard, Cecilia
Lasunción Ripa, Miguel A
López Rodríguez, María L.
Díaz-Laviada Marturet, Inés Cecilia|||0000-0001-9704-4373
author_role author
author2 Ortega Gutiérrez, Silvia
Viso, Alma
Sánchez Alonso, María de Gracia
Sánchez García, Ana María
Fernández, Carlos
Ramos, José A.
Hillard, Cecilia
Lasunción Ripa, Miguel A
López Rodríguez, María L.
Díaz-Laviada Marturet, Inés Cecilia|||0000-0001-9704-4373
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Anandamide degradation
Anandamide uptake inhibitors
Prostate PC-3 cells
Fatty acid amidohydrolase
Endogenous cannabinoid system
Biología y Biomedicina/Biología
Biology
topic Anandamide degradation
Anandamide uptake inhibitors
Prostate PC-3 cells
Fatty acid amidohydrolase
Endogenous cannabinoid system
Biología y Biomedicina/Biología
Biology
description 11 p.
publishDate 2004
dc.date.none.fl_str_mv 2004
2004-03-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10017/62380
https://dx.doi.org/10.1038/sj.bjp.0705628
url http://hdl.handle.net/10017/62380
https://dx.doi.org/10.1038/sj.bjp.0705628
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:e_Buah Biblioteca Digital Universidad de Alcalá
instname:Universidad de Alcalá (UAH)
instname_str Universidad de Alcalá (UAH)
reponame_str e_Buah Biblioteca Digital Universidad de Alcalá
collection e_Buah Biblioteca Digital Universidad de Alcalá
repository.name.fl_str_mv
repository.mail.fl_str_mv
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