Universidad Complutense de Madrid
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A Fluorescent Probe to Unravel Functional Features of Cannabinoid Receptor CB1 in Human Blood and Tonsil Immune System Cells

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Martín Fontecha, María del Mar y Angelina Querencias, Alba y Rückert, Beate y Rueda Zubiaurre, Ainoa y Martín Cruz, Leticia y Veen, Willem van de y Akdis, Mübeccel y Ortega Gutiérrez, Silvia y López Rodríguez, María Luz y Akdis, Cezmi A. y Palomares, Oscar (2018) A Fluorescent Probe to Unravel Functional Features of Cannabinoid Receptor CB1 in Human Blood and Tonsil Immune System Cells. Bioconjugate Chemistry, 29 (2). pp. 382-389. ISSN 1043-1802

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URL Oficial: https://doi.org/10.1021/acs.bioconjchem.7b00680




Resumen

The human endogenous cannabinoid system (ECS) regulates key physiological processes and alterations in its signaling pathways, and endocannabinoid levels are associated with diseases such as neurological and neuropsychiatric conditions, cancer, pain and inflammation, obesity, and metabolic and different immune related disorders. Immune system cells express the G-protein coupled cannabinoid receptor 1 (CB1), but its functional role has not been fully understood, likely due to the lack of appropriate tools. The availability of novel tools to investigate the role of CB1 in immune regulation might contribute to identify CB1 as a potential novel therapeutic target or biomarker for many diseases. Herein, we report the development and validation of the first fluorescent small molecule probe to directly visualize and quantify CB1 in blood and tonsil immune cells by flow cytometry and confocal microscopy. We coupled the cannabinoid agonist HU210 to the fluorescent tag Alexa Fluor 488, generating a fluorescent probe with high affinity for CB1 and selectivity over CB2. We validate HU210-Alexa488 for the rapid, simultaneous, and reproducible identification of CB1 in human monocytes, T cells, and B cells by multiplexed flow cytometry. This probe is also suitable for the direct visualization of CB1 in tonsil tissues, allowing the in vivo identification of tonsil CB1-expressing T and B cells. This study provides the first fluorescent chemical tool to investigate CB1 expression and function in human blood and tonsil immune cells, which might well pave the way to unravel essential features of CB1 in different immune and ECS-related diseases.


Tipo de documento:Artículo
Información Adicional:

Received 9 November 2017; Published online 9 January 2018; Published in print 21 February 2018

Palabras clave:Inmune system cells; Human blood; Cannabinoid receptor B1; Endogenous cannabinoid system; Disorders; Neurological disorders; CB1; Biomarker
Materias:Ciencias > Química > Bioquímica
Ciencias Biomédicas > Medicina > Fisiología
Ciencias Biomédicas > Medicina > Inmunología
Código ID:47251
Depositado:19 Abr 2018 13:41
Última Modificación:20 Abr 2018 07:47

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