Dataset Information

Menthol decreases oral nicotine aversion in C57BL/6 mice through a TRPM8-dependent mechanism.

ABSTRACT: Nicotine is a major oral irritant in smokeless tobacco products and has an aversive taste. Mentholated smokeless tobacco products are highly popular, suggesting that menthol increases their palatability and may facilitate initiation of product use. While menthol is known to reduce respiratory irritation by tobacco smoke irritants, it is not known whether this activity extends to oral nicotine and its aversive effects.The two-bottle choice drinking assay was used to characterise aversion and preference in C57BL/6 mice to a range of menthol concentrations (10-200?µg/mL). Then, effects of menthol on oral nicotine aversion were determined. Responses were compared with those in mice deficient in the cold/menthol receptor, TRPM8, expressed in trigeminal sensory neurons innervating the oral cavity.Mice showed aversion to menthol concentrations of 100?µg/mL and above. When presented with a highly aversive concentration of nicotine (200?µg/mL), mice preferred solutions with 50 or 100?µg/mL menthol added over nicotine alone. In contrast to wild-type mice, Trpm8-/- showed a strong aversion to mentholated (100?µg/mL) nicotine (200?µg/mL) and preferred nicotine alone. Trpm8-/- mice show aversion to lower concentrations of menthol than wild-type mice.Oral menthol can reduce the aversive effects of oral nicotine and, at higher concentrations, acts as an irritant by itself. Menthol's effects in relation to nicotine require TRPM8, the cool temperature sensing ion channel that activates analgesic and counterirritant mechanisms. These mechanisms may underlie preference for menthol-containing smokeless tobacco products and may facilitate initiation of product use.

SUBMITTER: Fan L

PROVIDER: S-EPMC5496986 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Menthol decreases oral nicotine aversion in C57BL/6 mice through a TRPM8-dependent mechanism.

Fan Lu L Balakrishna Shrilatha S Jabba Sairam V SV Bonner Pamela E PE Taylor Seth R SR Picciotto Marina R MR Jordt Sven-Eric SE

Tobacco control 20161003 Suppl 2

<h4>Background</h4>Nicotine is a major oral irritant in smokeless tobacco products and has an aversive taste. Mentholated smokeless tobacco products are highly popular, suggesting that menthol increases their palatability and may facilitate initiation of product use. While menthol is known to reduce respiratory irritation by tobacco smoke irritants, it is not known whether this activity extends to oral nicotine and its aversive effects.<h4>Study design</h4>The two-bottle choice drinking assay wa ...[more]

PMID: 27698211

Similar Datasets

Project description:Highlights • Tunica dartos smooth muscle (TDSM), which is responsible for scrotal thermoregulation, responds to cooling by enhancement of basal tension, and increase of the amplitude and duration of synaptically-evoked contractions.• TDSM cold-induced tension, but not synaptically-evoked contractions are sensitive to the blockers of TRPM8 cold/menthol receptor.• TRPM8 is localized to the TDSM cells' endoplasmic reticulum and its activation by cold causes intracellular calcium mobilization.• Chemical castration of male rats consequent to pharmacological blockade of androgen receptors eliminates the effects of cold on TDSM tension, but not on synaptically-evoked contractions, and abolishes TRPM8 protein expression.• TRPM8 is an important determinant of cold-dependent contractility of the tunica dartos muscle and scrotal thermoregulation which is crucial for maintaining normal spermatogenesis and male fertility. Tunica dartos smooth muscle (TDSM) lies beneath the scrotal skin, and its contraction leads to scrotum wrinkling upon cooling. However, neither the nature of TDSM cold-sensitivity nor the underlying molecular sensors are well understood. Here we have investigated the role of cold/menthol-sensitive TRPM8 channel in TDSM temperature-dependent contractility. The contraction of isolated male rat TDSM strips was studied by tensiometry. TRPM8 expression was assayed by RT-PCR and fluorescence immunochemistry. Isolated TDSM strips responded to cooling from 33 °C to 20 °C by enhancement of basal tension, and increase of the amplitude and duration of electric field stimulated (EFS) contractions. The effects of cold on basal tension, but not on EFS-contractions, could be 80% inhibited by TRPM8 blockers, capsazepine and BCTC [N-(4‑tert-butylphenyl)-4-(3-chloropyridin-2-yl)piperazine-1-carboxamide], and could be partially mimicked by menthol. RT-PCR and immunolabeling showed TRPM8 mRNA and protein expression in TDSM cells with protein labelling being predominantly localized to intracellular compartments. Chemical castration of male rats consequent to the treatment with androgen receptor blocker, flutamide, led to the abrogation of cold effects on TDSM basal tension, but not on EFS-contractions, and to the disappearance of TRPM8 protein expression. We conclude that TRPM8 is involved in the maintenance of basal cold-induced TDSM tonus, but not in sympathetic nerve-mediated contractility, by acting as endoplasmic reticulum Ca2+ release channel whose expression in TDSM cells requires the presence of a functional androgen receptor. Thus, TRPM8 plays a crucial role in scrotal thermoregulation which is important for maintaining normal spermatogenesis and male fertility.

Dataset Information

Menthol decreases oral nicotine aversion in C57BL/6 mice through a TRPM8-dependent mechanism.

Publications

Menthol decreases oral nicotine aversion in C57BL/6 mice through a TRPM8-dependent mechanism.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets