Peptide from Sea Anemone Metridium senile Affects Transient Receptor Potential Ankyrin-repeat 1 (TRPA1) Function and Produces Analgesic Effect

• Published in: The Journal of biological chemistry Vol. 292; no. 7; pp. 2992 - 3004
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17-02-2017; American Society for Biochemistry and Molecular Biology
• Subjects: Amino Acid Sequence; Analgesics - pharmacology; Animals; Base Sequence; Chemistry: 440; CHO Cells; Cricetulus; inflammation; Kjemi: 440; marine bioprospecting; Matematikk og Naturvitenskap: 400; Mathematics and natural science: 400; Mice; neuron; Organic chemistry: 441; Organisk kjemi: 441; pain; peptides; Peptides - chemistry; Peptides - isolation & purification; Peptides - pharmacology; potentiating effect; Protein Structure and Folding; receptor; sea anemones; Sea Anemones - chemistry; Sequence Homology, Amino Acid; Transient Receptor Potential Channels - drug effects; TRPA1; VDP; marine bioprospecting; potentiating effect; pain; receptor; TRPA1; inflammation; sea anemones; neuron; peptides
• ISSN: 0021-9258; 1083-351X; 1083-351X
• DOI: 10.1074/jbc.M116.757369

The transient receptor potential ankyrin-repeat 1 (TRPA1) is an important player in pain and inflammatory pathways. It is a promising target for novel drug development for the treatment of a number 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 τ-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. Peptide Ms 9a-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 anti-inflammatory effects in mice models of pain.