Lutein Inhibits the Function of the Transient Receptor Potential A1 Ion Channel in Different In Vitro and In Vivo Models
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Transient receptor potential (TRP) ion channels, such as TRP vanilloid 1 and ankyrin repeat domain 1 (TRPV1 and TRPA1), are expressed on primary sensory neurons. Lutein, a natural tetraterpene carotenoid, can be incorporated into membranes and might modulate TRP channels. Therefore, the effects of the water-soluble randomly methylated-β-cyclodextrin (RAMEB) complex of lutein were investigated on TRPV1 and TRPA1 activation. RAMEB–lutein (100 μM) significantly diminished Ca2+ influx to cultured rat trigeminal neurons induced by TRPA1 activation with mustard oil, but not by TRPV1 stimulation with capsaicin, as determined with microfluorimetry. Calcitonin gene-related peptide release from afferents of isolated tracheae evoked by mustard oil, but not by capsaicin, was inhibited by RAMEB–lutein. Mustard oil-induced neurogenic mouse ear swelling was also significantly decreased by 100 μg/ml s.c. RAMEB–lutein pretreatment, while capsaicin-evoked edema was not altered. Myeloperoxidase activity indicating non-neurogenic granulocyte accumulation in the ear was not influenced by RAMEB–lutein in either case. It is concluded that lutein inhibits TRPA1, but not TRPV1 stimulation-induced responses on cell bodies and peripheral terminals of sensory neurons in vitro and in vivo. Based on these distinct actions and the carotenoid structure, the ability of lutein to modulate lipid rafts in the membrane around TRP channels can be suggested.
KeywordsCalcitonin gene-related peptide (CGRP) Calcium imaging Carotenoids Cyclodextrin complex Lipid rafts Neurogenic inflammation
The authors thank Anikó Hirné Perkecz for the preparation of the histological slides and Dániel Tóth for technical assistance. Attila Dévay, the Head of Institute of Pharmaceutical Technology and Biopharmacy, for technical support. Our work was supported by OTKA K60121, K76176 K73044, K78059, ETT 03-380/2009, ETT 04-364/2009 and the “Science, Please! Research Teams on Innovation” programme (SROP-4.2.2/08/1/2008-0011) and Developing Competitiveness of Universities in the South Transdanubian Region (SROP-4.2.1.B-10/2/KONV-2010-0002). Györgyi Horváth was supported by PTE ÁOK KA-34039-35/2009 grant.
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