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Analysis of Structural Determinants of Peptide MS 9a-1 Essential for Potentiating of TRPA1 Channel

Authors :
Yulia A. Logashina
Kseniya I. Lubova
Ekaterina E. Maleeva
Viktor A. Palikov
Yulia A. Palikova
Igor A. Dyachenko
Yaroslav A. Andreev
Source :
Marine Drugs; Volume 20; Issue 7; Pages: 465
Publication Year :
2022

Abstract

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.

Details

ISSN :
16603397
Volume :
20
Issue :
7
Database :
OpenAIRE
Journal :
Marine drugs
Accession number :
edsair.doi.dedup.....e8a01a8b196b34b8f831ff864c3e7b2e