Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 292, Issue 7, Pages 2992-3004Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M116.757369
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Funding
- Russian Science Foundation [16-15-00167]
- Functional Genomics (FUGE) programme
- Biotek 2021 programme of the Research Council of Norway [208546]
- Russian Science Foundation [16-15-00167] Funding Source: Russian Science Foundation
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The transient receptor potential ankyrin-repeat 1 (TRPA1) is an important player in pain and inflammatory pathways. It is a prom-isingtargetfornoveldrugdevelopmentforthetreatmentofanum-ber of pathological states. A novel peptide producing a significant potentiating effect on allyl isothiocyanate-and diclofenac-induced currents of TRPA1 was isolated from the venom of sea anemone Metridium senile. It is a 35-amino acid peptide cross-linked by two disulfide bridges named tau-AnmTX Ms 9a-1 (short name Ms 9a-1) according to a structure similar to other sea anemone peptides belonging to structural group 9a. The structures of the two genes encoding the different precursor proteins of Ms 9a-1 were determined. PeptideMs9a-1 acted as a positive modulator of TRPA1 in vitro but did not cause pain or thermal hyperalgesia when injected into the hind paw of mice. Intravenous injection of Ms 9a-1 (0.3 mg/ kg) produced a significant decrease in the nociceptive and inflammatory response to allyl isothiocyanate (the agonist of TRPA1) and reversed CFA (Complete Freund's Adjuvant)-induced inflammation and thermal hyperalgesia. Taken together these data support the hypothesis that Ms 9a-1 potentiates the 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 a therapeutic approach as Ms 9a-1 produces significant analgesic and antiinflammatory effects in mice models of pain.
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