title: Peptide from Sea AnemoneMetridium senileAffects Transient Receptor Potential Ankyrin-repeat 1 (TRPA1) Function and Produces Analgesic Effect.
abstract: 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 anemoneMetridium 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 TRPA1in vitrobut 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.
authors.affiliation: From the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10,117997 Moscow, Russia.|the Sechenov First Moscow State Medical University, Institute of Molecular Medicine, Trubetskaya St. 8, Bldg. 2, 119991 Moscow, Russia.
authors.forename: Yulia A
authors.initials: YA
authors.lastname: Logashina
authors.affiliation: From the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10,117997 Moscow, Russia.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Mosharova
authors.affiliation: From the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10,117997 Moscow, Russia.
authors.forename: Yulia V
authors.initials: YV
authors.lastname: Korolkova
authors.affiliation: From the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10,117997 Moscow, Russia.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Shelukhina
authors.affiliation: the Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 6 Nauki Avenue, 142290 Pushchino, Moscow, Russia, and.
authors.forename: Igor A
authors.initials: IA
authors.lastname: Dyachenko
authors.affiliation: the Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 6 Nauki Avenue, 142290 Pushchino, Moscow, Russia, and.
authors.forename: Victor A
authors.initials: VA
authors.lastname: Palikov
authors.affiliation: the Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 6 Nauki Avenue, 142290 Pushchino, Moscow, Russia, and.
authors.forename: Yulia A
authors.initials: YA
authors.lastname: Palikova
authors.affiliation: the Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 6 Nauki Avenue, 142290 Pushchino, Moscow, Russia, and.
authors.forename: Arkadii N
authors.initials: AN
authors.lastname: Murashev
authors.affiliation: From the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10,117997 Moscow, Russia.
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Kozlov
authors.affiliation: the Norwegian College of Fishery Science, University of Tromsø, N9037 Tromsø, Norway.
authors.forename: Klara
authors.initials: K
authors.lastname: Stensvåg
authors.affiliation: From the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10,117997 Moscow, Russia, ay@land.ru.|the Sechenov First Moscow State Medical University, Institute of Molecular Medicine, Trubetskaya St. 8, Bldg. 2, 119991 Moscow, Russia.
authors.forename: Yaroslav A
authors.initials: YA
authors.lastname: Andreev
mesh_terms: D000595:Amino Acid Sequence; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D003412:Cricetulus; D051379:Mice; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D012615:Sea Anemones / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D050051:Transient Receptor Potential Channels / Q000187:drug effects*
chemical_list: D000700:Analgesics; D010455:Peptides; D050051:Transient Receptor Potential Channels
keywords: TRPA1; inflammation; marine bioprospecting; neuron; pain; peptides; potentiating effect; receptor; sea anemones