The monoterpene (–)‐carvone: A novel agonist of TRPV1 channels

Abstract

Abstract(-)-Carvone is an antinociceptive monoterpene found as the main active constituent of essential oils obtained from plants of the genus Mentha. Here, we have investigated the pharmacology of this monoterpene in dorsal root ganglia (DRG) neurons and TRPV1-expressing HEK293 cells. (-)-carvone at pharmacological active concentrations did not reveal significant cytotoxicity to the cells used in this study, as investigated by neutral red and propidium iodide flow cytometry assays. In calcium imaging experiments 1 mM (-)-carvone increased the cytosolic calcium levels in DRG neurons from 120.6 AE 5.0 nM (basal) to 310.7 AE 23.1 nM (P < 0.05). These effects were completely abolished when neurons were preincubated with calcium-free bath solution or ruthenium-red (5 mM) and capsazepine (10 mM), suggesting the possibility of TRPV1 channel-activation by (-)-carvone. Activity of (-)-carvone on TRPV1 channels was further investigated in HEK293 cells expressing recombinant human TRPV1 channels revealing dose-dependent calcium transients with an EC 50 of 1.3 AE 0.2 mM (Hill coefficient 5 2.5). In conclusion, we show for the first time the ability of (-)-carvone to induce increases in cytosolic calcium concentration through TRPV1 activation. ' 2013 International Society for Advancement of Cytometry

Involvement of transient receptor potential A1 channel in algesic and analgesic actions of the organic compound limonene

“…These results suggested that limonene acted as a TRPA1 agonist and elicits acute pain in mice through the activation of TRPA1. There are reports that some monoterpenes stimulate TRPV1 and/or TRPA1 (Xu et al, 2006;Xiao et al, 2008;Riera et al, 2009;Gonc ßalves et al, 2013) (Becker et al, 1990;Tsung-Hung et al, 2002). However, it is unlikely that an indirect action of H 2 O 2 is involved in the stimulatory effects of limonene on TRPA1, since the H 2 O 2 level in limonene-containing aqueous solution was in the submicromolar range, a concentration insufficient for TRPA1 activation (Takahashi et al, 2008).…”

Local Anaesthetic Properties vs. Neurotoxicity for (+)- and (−)-Carvone: An Ex Vivo Electrophysiological Study

“…The same mechanism has been proposed for the local anaesthetic action of linalool [18]. Yet another mechanism was proposed for the action of (−)-carvone, which was recently identified as a novel agonist of TRPV-1 channels [9], thus being a promising target for the development of analgesic drugs [10,11]. Although the mechanism of inhibition of the action potential by carvones is not clear, there is already a number of publications suggesting their use as local anaesthetics.…”

“…Ex vivo electrophysiological data indicate that both enantiomers of carvone are able to inhibit the nerve-evoked CAP of the isolated sciatic nerve of Wistar rats and of the frog [4,5], in a concentration-dependent manner and in an almost reversible way [6]. Recently, (−)-carvone was reported as a novel agonist of TRPV-1 channels [9], and thus a promising target for the development of analgesic drugs [10,11]. Since carvone-producing plants are used in everyday life and in medicine, information on the mode of their action is crucial and can contribute to the development of new compounds with desired properties.…”

Involvement of nucleotides in glial growth following scratch injury in avian retinal cell monolayer cultures

“…The Fluo-3 AM indicator was used, following previous published protocols [31,32]. In brief, cultures were incubated for 1 h in complete MEM medium containing 5 μM Fluo-3 AM, 0.2 % (v/v) Pluronic F-127, 0.5 % (v/v) DMSO, and 2.5 mM probenecid.…”