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Peptide from sea anemone metridium senile affects transient receptor potential ankyrin-repeat 1 (TRPA1) function and produces analgesic effect

Permanent lenke
https://hdl.handle.net/10037/13816
DOI
https://doi.org/10.1074/jbc.M116.757369
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article.pdf (1.853Mb)
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Dato
2017-01-11
Type
Journal article
Tidsskriftartikkel
Peer reviewed

Forfatter
Logashina, Yulia A.; Mosharova, Irina V.; Korolkova, Yulia V.; Shelukhina, Irina V; Dyachenko, Igor A.; Palikov, Victor A.; Palikova, Yulia A.; Murashev, Arkadii N.; Kozlov, Sergey A.; Stensvåg, Klara; Andreev, Yaroslav A.
Sammendrag
The Transient Receptor Potential Ankyrin-repeat 1 (TRPA1) is an important player in pain and inflammatory pathways. It is a promising target for novel drugs development for treatment of a number of pathological states. A novel peptide producing significant potentiating effect (up to ~90%) on AITC- and diclofenac-induced currents of TRPA1 was isolated from the venom of sea anemone Metridium senile. It is 35 amino acid peptide cross-linked by two disulfide bridges, named τ-AnmTX Ms 9a-1 (short name Ms 9a-1) according to structure similarity to other sea anemone peptides belonging to structural group 9a. The structure of two genes encoding different precursor proteins of Ms 9a-1 were determined. Peptide Ms 9a-1 acted as a positive modulator of TRPA1 in vitro but did not cause pain or thermal hyperalgesia when injected in mice hind paw. Intravenous injection of Ms 9a-1 (0.3 mg/kg) produced significant decrease of nociceptive and inflammatory response to AITC (agonist of TRPA1) and reversed CFA-induced inflammation and thermal hyperalgesia. Taken together, these data support the hypothesis that Ms 9a-1 potentiates response of TRPA1 to endogenous agonists followed by persistent functional loss of TRPA1-expressing neurons. We can conclude that TRPA1 potentiating may be useful as therapeutic approach since Ms 9a-1 produce significant analgesic and anti- inflammatory effect in mice models of pain.
Beskrivelse
Source at: http://doi.org/10.1074/jbc.M116.757369
Forlag
American Society for Biochemistry and Molecular Biology
Sitering
Logashina, Y. A., Mosharova, I. V., Korolkova, Y. V., Shelukhina, I. V., Dyachenko, I. A., Palikov, V. A. ... Andreev, Y. A. (2017). Peptide from sea anemone metridium senile affects transient receptor potential ankyrin-repeat 1 (TRPA1) function and produces analgesic effect. Journal of Biological Chemistry, 292(7), 2992-3004. http://doi.org/10.1074/jbc.M116.757369
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