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Carboxamido steroids inhibit the opening properties of transient receptor potential ion channels by lipid raft modulation
Transient Receptor Potential (TRP) cation channels, like the TRP Vanilloid 1 (TRPV1) and TRP Ankyrin 1 (TRPA1), are expressed on primary sensory neurons. These thermosensor channels play a role in pain processing. We have provided evidence previously that lipid raft disruption influenced the TRP cha...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Biochemistry and Molecular Biology
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168298/ https://www.ncbi.nlm.nih.gov/pubmed/30093524 http://dx.doi.org/10.1194/jlr.M084723 |
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author | Sághy, Éva Payrits, Maja Bíró-Sütő, Tünde Skoda-Földes, Rita Szánti-Pintér, Eszter Erostyák, János Makkai, Géza Sétáló, György Kollár, László Kőszegi, Tamás Csepregi, Rita Szolcsányi, János Helyes, Zsuzsanna Szőke, Éva |
author_facet | Sághy, Éva Payrits, Maja Bíró-Sütő, Tünde Skoda-Földes, Rita Szánti-Pintér, Eszter Erostyák, János Makkai, Géza Sétáló, György Kollár, László Kőszegi, Tamás Csepregi, Rita Szolcsányi, János Helyes, Zsuzsanna Szőke, Éva |
author_sort | Sághy, Éva |
collection | PubMed |
description | Transient Receptor Potential (TRP) cation channels, like the TRP Vanilloid 1 (TRPV1) and TRP Ankyrin 1 (TRPA1), are expressed on primary sensory neurons. These thermosensor channels play a role in pain processing. We have provided evidence previously that lipid raft disruption influenced the TRP channel activation, and a carboxamido-steroid compound (C1) inhibited TRPV1 activation. Therefore, our aim was to investigate whether this compound exerts its effect through lipid raft disruption and the steroid backbone (C3) or whether altered position of the carboxamido group (C2) influences the inhibitory action by measuring Ca(2+) transients on isolated neurons and calcium-uptake on receptor-expressing CHO cells. Membrane cholesterol content was measured by filipin staining and membrane polarization by fluorescence spectroscopy. Both the percentage of responsive cells and the magnitude of the intracellular Ca(2+) enhancement evoked by the TRPV1 agonist capsaicin were significantly inhibited after C1 and C2 incubation, but not after C3 administration. C1 was able to reduce other TRP channel activation as well. The compounds induced cholesterol depletion in CHO cells, but only C1 induced changes in membrane polarization. The inhibitory action of the compounds on TRP channel activation develops by lipid raft disruption, and the presence and the position of the carboxamido group is essential. |
format | Online Article Text |
id | pubmed-6168298 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-61682982018-10-03 Carboxamido steroids inhibit the opening properties of transient receptor potential ion channels by lipid raft modulation Sághy, Éva Payrits, Maja Bíró-Sütő, Tünde Skoda-Földes, Rita Szánti-Pintér, Eszter Erostyák, János Makkai, Géza Sétáló, György Kollár, László Kőszegi, Tamás Csepregi, Rita Szolcsányi, János Helyes, Zsuzsanna Szőke, Éva J Lipid Res Research Articles Transient Receptor Potential (TRP) cation channels, like the TRP Vanilloid 1 (TRPV1) and TRP Ankyrin 1 (TRPA1), are expressed on primary sensory neurons. These thermosensor channels play a role in pain processing. We have provided evidence previously that lipid raft disruption influenced the TRP channel activation, and a carboxamido-steroid compound (C1) inhibited TRPV1 activation. Therefore, our aim was to investigate whether this compound exerts its effect through lipid raft disruption and the steroid backbone (C3) or whether altered position of the carboxamido group (C2) influences the inhibitory action by measuring Ca(2+) transients on isolated neurons and calcium-uptake on receptor-expressing CHO cells. Membrane cholesterol content was measured by filipin staining and membrane polarization by fluorescence spectroscopy. Both the percentage of responsive cells and the magnitude of the intracellular Ca(2+) enhancement evoked by the TRPV1 agonist capsaicin were significantly inhibited after C1 and C2 incubation, but not after C3 administration. C1 was able to reduce other TRP channel activation as well. The compounds induced cholesterol depletion in CHO cells, but only C1 induced changes in membrane polarization. The inhibitory action of the compounds on TRP channel activation develops by lipid raft disruption, and the presence and the position of the carboxamido group is essential. The American Society for Biochemistry and Molecular Biology 2018-10 2018-08-09 /pmc/articles/PMC6168298/ /pubmed/30093524 http://dx.doi.org/10.1194/jlr.M084723 Text en Copyright © 2018 Sághy et al. Published by The American Society for Biochemistry and Molecular Biology, Inc. http://creativecommons.org/licenses/by/4.0/ Author’s Choice—Final version open access under the terms of the Creative Commons CC-BY license. |
spellingShingle | Research Articles Sághy, Éva Payrits, Maja Bíró-Sütő, Tünde Skoda-Földes, Rita Szánti-Pintér, Eszter Erostyák, János Makkai, Géza Sétáló, György Kollár, László Kőszegi, Tamás Csepregi, Rita Szolcsányi, János Helyes, Zsuzsanna Szőke, Éva Carboxamido steroids inhibit the opening properties of transient receptor potential ion channels by lipid raft modulation |
title | Carboxamido steroids inhibit the opening properties of transient receptor potential ion channels by lipid raft modulation |
title_full | Carboxamido steroids inhibit the opening properties of transient receptor potential ion channels by lipid raft modulation |
title_fullStr | Carboxamido steroids inhibit the opening properties of transient receptor potential ion channels by lipid raft modulation |
title_full_unstemmed | Carboxamido steroids inhibit the opening properties of transient receptor potential ion channels by lipid raft modulation |
title_short | Carboxamido steroids inhibit the opening properties of transient receptor potential ion channels by lipid raft modulation |
title_sort | carboxamido steroids inhibit the opening properties of transient receptor potential ion channels by lipid raft modulation |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168298/ https://www.ncbi.nlm.nih.gov/pubmed/30093524 http://dx.doi.org/10.1194/jlr.M084723 |
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