Peptide from Sea Anemone Metridium senile Affects 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 anemone 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 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.

Marine natural products

“…574 A 35-amino-acid peptide containing two disulde bridges Ms 9a-1, isolated from the venom of the sea anemone Metridium senile, produced signicant potentiating effect on the transient receptor potential ankyrin-repeat 1 (TRPA1) implying utility as an analgesic or anti-inammatory agent. 575 Crassicorin-I and putative homologue crassicorin-II were isolated from pharynx extracts of the anemone Urticina crassicornis. 576 Recombinant crassicorin-I was an antimicrobial peptide (AMP) exhibiting activity towards both Gram-positive and -negative bacteria, with its transcript being upregulated by immune challenge, implying a defensive role.…”

Pain-Causing Venom Peptides: Insights into Sensory Neuron Pharmacology

“…TRPA1 initiates pain signalling due to inflammatory mediators and noxious cold, and has a well-established role in toxin-induced pain [ 22 ]. Interestingly, no algesic venom peptide activator of TRPA1 has been described, although several peptides elicit analgesic effects via inhibition or activation-induced desensitisation of this channel [ 63 , 64 , 65 , 66 ].…”

“…Similarly, Phα1β ( Phoneutria nigriventer ) is a Ca V and TRPA1 antagonist, and has been shown to attenuate mechanical and cold hyperalgesia induced by the TRPA1 agonist allyl isothiocyanate (AITC) in vivo [ 65 ]. On the other hand, the sea anemone venom peptide Ms 9a-1 is a positive modulator for TRPA1 in vitro and produces analgesic and anti-inflammatory responses in vivo, possibly via a desensitisation mechanism [ 66 ]. Similarly, crotalphine, a small venom peptide from a South American rattlesnake ( Crotalus durissus terrificus ), is a partial activator of TRPA1 and causes strong desensitisation of the channel, which may be responsible for its analgesic effect in vivo [ 64 , 67 ].…”

A Low Molecular Weight Protein from the Sea Anemone Anemonia viridis with an Anti-Angiogenic Activity

“…They have toxic peptides to incapacitate and immobilize prey and to defend from potential predators [ 2 ]. Their toxin arsenal is complex, targeting a variety of pharmacological targets such as ionic channels, inflammatory receptors [ 3 ] or pore forming protein in cellular membranes [ 4 ]. Anti-hyperglycemic and anti-diabetic activities were also observed from sea anemone extract [ 5 ].…”