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Analysis of Structural Determinants of Peptide MS 9a-1 Essential for Potentiating of TRPA1 Channel
The TRPA1 channel is involved in a variety of physiological processes and its activation leads to pain perception and the development of inflammation. Peptide Ms 9a-1 from sea anemone Metridium senile is a positive modulator of TRPA1 and causes significant analgesic and anti-inflammatory effects by...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320628/ https://www.ncbi.nlm.nih.gov/pubmed/35877758 http://dx.doi.org/10.3390/md20070465 |
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author | Logashina, Yulia A. Lubova, Kseniya I. Maleeva, Ekaterina E. Palikov, Viktor A. Palikova, Yulia A. Dyachenko, Igor A. Andreev, Yaroslav A. |
author_facet | Logashina, Yulia A. Lubova, Kseniya I. Maleeva, Ekaterina E. Palikov, Viktor A. Palikova, Yulia A. Dyachenko, Igor A. Andreev, Yaroslav A. |
author_sort | Logashina, Yulia A. |
collection | PubMed |
description | The TRPA1 channel is involved in a variety of physiological processes and its activation leads to pain perception and the development of inflammation. Peptide Ms 9a-1 from sea anemone Metridium senile is a positive modulator of TRPA1 and causes significant analgesic and anti-inflammatory effects by desensitization of TRPA1-expressing sensory neurons. For structural and functional analysis of Ms 9a-1, we produced four peptides—Ms 9a-1 without C-terminal domain (abbreviated as N-Ms), short C-terminal domain Ms 9a-1 alone (C-Ms), and two homologous peptides (Ms 9a-2 and Ms 9a-3). All tested peptides possessed a reduced potentiating effect on TRPA1 compared to Ms 9a-1 in vitro. None of the peptides reproduced analgesic and anti-inflammatory properties of Ms 9a-1 in vivo. Peptides N-Ms and C-Ms were able to reduce pain induced by AITC (selective TRPA1 agonist) but did not decrease AITC-induced paw edema development. Fragments of Ms 9a-1 did not effectively reverse CFA-induced thermal hyperalgesia and paw edema. Ms 9a-2 and Ms 9a-3 possessed significant effects and anti-inflammatory properties in some doses, but their unexpected efficacy and bell-shape dose–responses support the hypothesis of other targets involved in their effects in vivo. Therefore, activity comparison of Ms 9a-1 fragments and homologues peptides revealed structural determinants important for TRPA1 modulation, as well as analgesic and anti-inflammatory properties of Ms9a-1. |
format | Online Article Text |
id | pubmed-9320628 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-93206282022-07-27 Analysis of Structural Determinants of Peptide MS 9a-1 Essential for Potentiating of TRPA1 Channel Logashina, Yulia A. Lubova, Kseniya I. Maleeva, Ekaterina E. Palikov, Viktor A. Palikova, Yulia A. Dyachenko, Igor A. Andreev, Yaroslav A. Mar Drugs Article The TRPA1 channel is involved in a variety of physiological processes and its activation leads to pain perception and the development of inflammation. Peptide Ms 9a-1 from sea anemone Metridium senile is a positive modulator of TRPA1 and causes significant analgesic and anti-inflammatory effects by desensitization of TRPA1-expressing sensory neurons. For structural and functional analysis of Ms 9a-1, we produced four peptides—Ms 9a-1 without C-terminal domain (abbreviated as N-Ms), short C-terminal domain Ms 9a-1 alone (C-Ms), and two homologous peptides (Ms 9a-2 and Ms 9a-3). All tested peptides possessed a reduced potentiating effect on TRPA1 compared to Ms 9a-1 in vitro. None of the peptides reproduced analgesic and anti-inflammatory properties of Ms 9a-1 in vivo. Peptides N-Ms and C-Ms were able to reduce pain induced by AITC (selective TRPA1 agonist) but did not decrease AITC-induced paw edema development. Fragments of Ms 9a-1 did not effectively reverse CFA-induced thermal hyperalgesia and paw edema. Ms 9a-2 and Ms 9a-3 possessed significant effects and anti-inflammatory properties in some doses, but their unexpected efficacy and bell-shape dose–responses support the hypothesis of other targets involved in their effects in vivo. Therefore, activity comparison of Ms 9a-1 fragments and homologues peptides revealed structural determinants important for TRPA1 modulation, as well as analgesic and anti-inflammatory properties of Ms9a-1. MDPI 2022-07-21 /pmc/articles/PMC9320628/ /pubmed/35877758 http://dx.doi.org/10.3390/md20070465 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Logashina, Yulia A. Lubova, Kseniya I. Maleeva, Ekaterina E. Palikov, Viktor A. Palikova, Yulia A. Dyachenko, Igor A. Andreev, Yaroslav A. Analysis of Structural Determinants of Peptide MS 9a-1 Essential for Potentiating of TRPA1 Channel |
title | Analysis of Structural Determinants of Peptide MS 9a-1 Essential for Potentiating of TRPA1 Channel |
title_full | Analysis of Structural Determinants of Peptide MS 9a-1 Essential for Potentiating of TRPA1 Channel |
title_fullStr | Analysis of Structural Determinants of Peptide MS 9a-1 Essential for Potentiating of TRPA1 Channel |
title_full_unstemmed | Analysis of Structural Determinants of Peptide MS 9a-1 Essential for Potentiating of TRPA1 Channel |
title_short | Analysis of Structural Determinants of Peptide MS 9a-1 Essential for Potentiating of TRPA1 Channel |
title_sort | analysis of structural determinants of peptide ms 9a-1 essential for potentiating of trpa1 channel |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320628/ https://www.ncbi.nlm.nih.gov/pubmed/35877758 http://dx.doi.org/10.3390/md20070465 |
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