TRPV1 is a novel target for omega-3 polyunsaturated fatty acids.

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Matta JA, Miyares RL, Ahern GP

TRPV1 is a novel target for omega-3 polyunsaturated fatty acids.

J Physiol. 2007 Jan 15;578(Pt 2):397-411. Epub 2006 Oct 12.

PubMed ID

17038422 [ View in PubMed

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Abstract

Omega-3 (n-3) fatty acids are essential for proper neuronal function, and they possess prominent analgesic properties, yet their underlying signalling mechanisms are unclear. Here we show that n-3 fatty acids interact directly with TRPV1, an ion channel expressed in nociceptive neurones and brain. These fatty acids activate TRPV1 in a phosphorylation-dependent manner, enhance responses to extracellular protons, and displace binding of the ultrapotent TRPV1 ligand [3H]resiniferatoxin. In contrast to their agonistic properties, n-3 fatty acids competitively inhibit the responses of vanilloid agonists. These actions occur in mammalian cells in the physiological concentration range of 1-10 mum. Significantly, docosahexaenoic acid exhibits the greatest efficacy as an agonist, whereas eicosapentaenoic acid and linolenic acid are markedly more effective inhibitors. Similarly, eicosapentaenoic acid but not docosahexaenoic acid profoundly reduces capsaicin-evoked pain-related behaviour in mice. These effects are independent of alterations in membrane elasticity because the micelle-forming detergent Triton X-100 only minimally affects TRPV1 properties. Thus, n-3 fatty acids differentially regulate TRPV1 and this form of signalling may contribute to their biological effects. Further, these results suggest that dietary supplementation with selective n-3 fatty acids would be most beneficial for the treatment of pain.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
alpha-Linolenic acid	Transient receptor potential cation channel subfamily V member 1	Protein	Humans	Yes	Inhibitor	Details
Icosapent	Transient receptor potential cation channel subfamily V member 1	Protein	Humans	Unknown	Inducer	Details