Miogadial and miogatrial with alpha,beta-unsaturated 1,4-dialdehyde moieties--novel and potent TRPA1 agonists

Life Sci. 2009 Jul 3;85(1-2):60-9. doi: 10.1016/j.lfs.2009.04.017. Epub 2009 May 3.

Abstract

Aims: Most of the terpenoids with an alpha,beta-unsaturated 1,4-dialdehyde moiety, which are found in plants, fungi, and insects, have a pungent taste. However, the neural receptors responsible for the pungency of these terpenoids have not been identified yet. The transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1), which are expressed in the nociceptive neurons, induce a sensation of heat on activation by some pungent ingredients in food. In this study, we selected miogadial (MD), miogatrial (MT), and polygodial (PG) from the terpenoids with an alpha,beta-unsaturated 1,4-dialdehyde moiety and examined the effects of these 3 terpenoids on TRPA1 or TRPV1.

Main methods: TRPV1 and TRPA1 activity by 3 terpenoids were evaluated using Ca(2+) imaging and patch-clamp methods in mammalian cells that express TRP heterologously and mouse sensory neurons.

Key findings: The 3 terpenoids activated TRPA1 that was heterologously expressed in HEK293 or CHO cells. The potencies of activation by the 3 terpenoids were equal and almost 10 times stronger than that of allyl isothiocyanate (AITC), which is known as the most potent TRPA1 agonist among all natural products. Moreover, these 3 terpenoids exhibited increased intracellular Ca(2+) concentration in mouse sensory neuron cells compared to AITC. High concentrations of the 3 terpenoids also activated TRPV1 that was heterologously expressed in HEK293 cells.

Significance: These results indicated that MD, MT, and PG were more potent in activating TRPA1 than TRPV1, and suggested that they primarily activate TRPA1 to induce pungency.

MeSH terms

  • Aldehydes / chemistry*
  • Animals
  • Behavior, Animal / drug effects
  • CHO Cells
  • Calcium / metabolism
  • Cell Line
  • Cricetinae
  • Cricetulus
  • Diterpenes / chemistry*
  • Diterpenes / pharmacology*
  • Electrophysiology
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / drug effects
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pain / psychology
  • Sensory Receptor Cells / drug effects
  • Sesquiterpenes / pharmacology
  • Structure-Activity Relationship
  • TRPA1 Cation Channel
  • TRPV Cation Channels / agonists
  • Transient Receptor Potential Channels / agonists*

Substances

  • 12-labdene-15,16,(8)17-trial
  • Aldehydes
  • Diterpenes
  • Sesquiterpenes
  • TRPA1 Cation Channel
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • Transient Receptor Potential Channels
  • Trpa1 protein, mouse
  • miogadial
  • polygodial
  • Calcium