TRPA1-dependent reversible opening of tight junction by natural compounds with an α,ß-unsaturated moiety and capsaicin.
Sci Rep
; 8(1): 2251, 2018 02 02.
Article
em En
| MEDLINE
| ID: mdl-29396565
ABSTRACT
The delivery of hydrophilic macromolecules runs into difficulties such as penetration of the cell membrane lipid bilayer. Our prior experiment demonstrated that capsaicin induces the reversible opening of tight junctions (TJs) and enhances the delivery of hydrophilic macromolecules through a paracellular route. Herein, we screened paracellular permeability enhancers other than capsaicin. As TJ opening by capsaicin is associated with Ca2+ influx, we first screened the compounds that induce Ca2+ influx in layered MDCK II cells, and then we determined the compounds' abilities to open TJs. Our results identified several natural compounds with α,ß-unsaturated moiety. A structure-activity relationship (SAR) analysis and the results of pretreatment with reducing reagent DTT suggested the importance of α,ß-unsaturated moiety. We also examined the underlying mechanisms, and our findings suggest that the actin reorganization seen in capsaicin treatment is important for the reversibility of TJ opening. Furthermore, our analyses revealed that TRPA1 is involved in the Ca2+ influx and TJ permeability increase not only by an α,ß-unsaturated compound but also by capsaicin. Our results indicate that the α,ß-unsaturated moiety can be a potent pharmacophore for TJ opening.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Permeabilidade
/
Capsaicina
/
Junções Íntimas
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Canal de Cátion TRPA1
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article