title: Inhibition by TRPA1 agonists of compound action potentials in the frog sciatic nerve.
abstract: Although TRPV1 and TRPM8 agonists (vanilloid capsaicin and menthol, respectively) at high concentrations inhibit action potential conduction, it remains to be unknown whether TRPA1 agonists have a similar action. The present study examined the actions of TRPA1 agonists, cinnamaldehyde (CA) and allyl isothiocyanate (AITC), which differ in chemical structure from each other, on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. CA and AITC concentration-dependently reduced the peak amplitude of the CAP with the IC50 values of 1.2 and 1.5mM, respectively; these activities were resistant to a non-selective TRP antagonist ruthenium red or a selective TRPA1 antagonist HC-030031. The CA and AITC actions were distinct in property; the latter but not former action was delayed in onset and partially reversible, and CA but not AITC increased thresholds to elicit CAPs. A CAP inhibition was seen by hydroxy-α-sanshool (by 60% at 0.05 mM), which activates both TRPA1 and TRPV1 channels, a non-vanilloid TRPV1 agonist piperine (by 20% at 0.07 mM) and tetrahydrolavandulol (where the six-membered ring of menthol is opened; IC50=0.38 mM). It is suggested that TRPA1 agonists as well as TRPV1 and TRPM8 agonists have an ability to inhibit nerve conduction without TRP activation, although their agonists are quite different in chemical structure from each other.
authors.affiliation: Department of Physiology, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan.
authors.forename: Akitomo
authors.initials: A
authors.lastname: Matsushita
authors.forename: Sena
authors.initials: S
authors.lastname: Ohtsubo
authors.forename: Tsugumi
authors.initials: T
authors.lastname: Fujita
authors.forename: Eiichi
authors.initials: E
authors.lastname: Kumamoto
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects*; D000080462:Acyclic Monoterpenes; D000470:Alkaloids / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D000818:Animals; D052117:Benzodioxoles / Q000494:pharmacology; D005260:Female; D017879:Isothiocyanates / Q000494:pharmacology; D008297:Male; D039821:Monoterpenes / Q000494:pharmacology; D009431:Neural Conduction / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D011898:Ranidae; D012584:Sciatic Nerve / Q000187:drug effects* / Q000378:metabolism*; D050051:Transient Receptor Potential Channels / Q000819:agonists*
chemical_list: D000080462:Acyclic Monoterpenes; D000470:Alkaloids; D000577:Amides; D052117:Benzodioxoles; D017879:Isothiocyanates; D039821:Monoterpenes; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D050051:Transient Receptor Potential Channels; C100574:sanshool; D000171:Acrolein; C004471:allyl isothiocyanate; C012843:cinnamaldehyde; C492921:lavandulol; C008922:piperine