Menthol and Related Cooling Compounds

Eccles, Ronald

doi:10.1111/j.2042-7158.1994.tb03871.x

Cited by 425 publications

(354 citation statements)

References 75 publications

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“…Activation of the capsaicin, nicotine, and menthol receptors, respectively, is accomplished by chemicals possessing defined structural requirements (Eccles 1994;Walpole et al 1996;Alimohammadi and Silver 2000). In agreement with this, specific blockage of nicotinic nasal trigeminal receptors seems to leave sensitivity to unrelated volatile organic compounds (VOCs) intact (Alimohammadi and Silver 2000).…”

Section: Introductionmentioning

confidence: 85%

Chemosensory additivity in trigeminal chemoreception as reflected by detection of mixtures

2004

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A series of experiments probed into the degree of chemosensory detection additivity exhibited by mixtures of ethyl propanoate and heptanoate in terms of their trigeminal detectability via nasal pungency (i.e., irritation) and eye irritation. Nasal pungency was tested in subjects lacking a functional sense of smell (i.e., anosmics) to avoid olfactory biases. First, we built concentrationdetection functions for each chemical and sensory endpoint. Second, we used the data from the functions to prepare mixtures of the two compounds in complementary proportions, and suitable single-chemical standards, all of which should be equally detectable under a rule of complete additivity, i.e., independence of detection. Third, we compared the experimentally obtained detectability with that expected under such rule. The outcome revealed that, at a low detectability level (but still above chance), the mixtures showed complete additivity for both trigeminal endpoints. At a high detectability level (but below perfect detection), the mixtures showed complete additivity for nasal pungency but less than complete additivity for eye irritation. In the context of previous studies, the results consolidate a picture of higher degree of detection additivity at perithreshold levels in trigeminal than in olfactory chemoreception. The outcome presents another line of evidence suggesting broader chemical tuning in chemesthesis compared to olfaction.

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Section: Introductionmentioning

confidence: 85%

Chemosensory additivity in trigeminal chemoreception as reflected by detection of mixtures

2004

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“…Menthol (C 10 H 19 OH), a monocyclic terpene alcohol derived from both natural and synthetic sources, is used as a flavoring agent in cigarettes and other consumer products [9][10][11]. Menthol cigarettes are manufactured by spraying this additive on tobacco, applying it to the packaging foil, or introducing it into the filter [12].…”

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confidence: 99%

The lingering question of menthol in cigarettes

Besaratinia

Tommasi

2014

Cancer Causes Control

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Tobacco use is the single most important preventable cause of cancer-related deaths in the USA and many parts of the world. There is growing evidence that menthol cigarettes are starter tobacco products for children, adolescents, and young adults. Accumulating research also suggests that smoking menthol cigarettes reinforces nicotine dependence, impedes cessation, and promotes relapse. However, menthol cigarettes are exempt from the US Food and Drug Administration ban on flavored cigarettes due, in part, to the lack of empirical evidence describing the health consequences of smoking menthol cigarettes relative to regular cigarettes. Determining the biological effects of menthol cigarette smoke relative to regular cigarette smoke can clarify the health risks associated with the use of respective products and assist regulatory agencies in making scientifically based decisions on the development and evaluation of regulations on tobacco products to protect public health and to reduce tobacco use by minors. We highlight the inherent shortcomings of the conventional epidemiologic, clinical, and laboratory research on menthol cigarettes that have contributed to the ongoing debate on the public health impact of menthol in cigarettes. In addition, we provide perspectives on how future investigations exploiting state-of-the-art biomarkers of exposure and disease states can help answer the lingering question of menthol in cigarettes.With the enactment of the Family Smoking Prevention and Tobacco Control Act (FSPTCA) in 2009, the US Food and Drug Administration (FDA) was granted authority to regulate the manufacture, marketing, and distribution of tobacco products to protect public health and to reduce tobacco use by minors [1]. In 2011, the Tobacco Products Scientific Advisory Committee (TPSAC) reported to the FDA that ''menthol cigarettes damage public health,'' and recommended that ''removal of menthol cigarettes would benefit public health in the USA'' [2]. The TPSAC report has been substantiated by ample research, suggesting that smoking menthol cigarettes is a ''gateway'' to using other tobacco products, especially during childhood and early adulthood, increases nicotine addiction, deters quitting, and promotes relapse [3,4]. Because smoking is our nation's leading cause of preventable death [5,6], any ingredient that may encourage people to take up this deadly habit or reinforce this lethal addiction should be considered a significant public health concern. However, the FDA has not yet taken regulatory steps, including imposing a ban on menthol cigarettes despite banning all the other flavored cigarettes from the US market [1]. This lack of action may, in part, be due to the absence of empirical evidence describing the health consequences of smoking menthol cigarettes relative to regular cigarettes [7,8]. Finding scientific underpinnings for the adverse health effects of smoking menthol cigarettes relative to regular cigarettes is of significance because it can help advance the FDA's mission of developing an...

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“…The soothing, refreshing and invigorating feature of the oil made from the peppermint herb is useful in massage for muscle fatigue. It is also used in the treatment of asthma, colic, exhaustion, fever, flatulence, headache, nausea, scabies, sinusitis, and vertigo (1). Currently the best described molecular target of menthol is TRPM8, 2 a member of the melastatin branch of the TRP superfamily of cation channels.…”

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confidence: 99%

TRPM8-independent Menthol-induced Ca2+ Release from Endoplasmic Reticulum and Golgi

Mahieu

Owsianik

Verbert

et al. 2007

Journal of Biological Chemistry

120

105

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Menthol, a secondary alcohol produced by the peppermint herb, Mentha piperita, is widely used in the food and pharmaceutical industries as a cooling/soothing compound and odorant. It induces Ca 2؉ influx in a subset of sensory neurons from dorsal root and trigeminal ganglia, due to activation of TRPM8, a Ca 2؉ -permeable, cold-activated member of the TRP superfamily of cation channels. Menthol also induces Ca 2؉ release from intracellular stores in several TRPM8-expressing cell types, which has led to the suggestion that TRPM8 can function as an intracellular Ca 2؉ -release channel. Here we show that menthol induces Ca 2؉ release from intracellular stores in four widely used cell lines (HEK293, lymph node carcinoma of the prostate (LNCaP), Chinese hamster ovary (CHO), and COS), and provide several lines of evidence indicating that this release pathway is TRPM8-independent: 1) menthol-induced Ca 2؉ release was potentiated at higher temperatures, which contrasts to the cold activation of TRPM8; 2) overexpression of TRPM8 did not enhance the menthol-induced Ca 2؉ release; 3) menthol-induced Ca 2؉ release was mimicked by geraniol and linalool, which are structurally related to menthol, but not by the more potent TRPM8 agonists icilin or eucalyptol; and 4) TRPM8 expression in HEK293 cells was undetectable at the protein and mRNA levels. Moreover, using a novel TRPM8-specific antibody we demonstrate that both heterologously expressed TRPM8 (in HEK293 cells) and endogenous TRPM8 (in LNCaP cells) are mainly localized in the plasma membrane, which contrast to previous localization studies using commercial anti-TRPM8 antibodies. Finally, aequorin-based measurements demonstrate that the TRPM8-independent menthol-induced Ca 2؉ release originates from both endoplasmic reticulum and Golgi compartments.Menthol is a naturally occurring compound responsible for the minty flavor and smell of the mint plant (Mentha piperita). Whereas the first descriptions of the use of menthol as a cooling/soothing compound and odorant date back to ϳ2000 years ago, menthol is still extensively used as an additive in a wide variety of products ranging from ointments and candies to cigarettes. The soothing, refreshing and invigorating feature of the oil made from the peppermint herb is useful in massage for muscle fatigue. It is also used in the treatment of asthma, colic, exhaustion, fever, flatulence, headache, nausea, scabies, sinusitis, and vertigo (1). Currently the best described molecular target of menthol is TRPM8, 2 a member of the melastatin branch of the TRP superfamily of cation channels. TRPM8 was initially identified in a screening procedure aimed at identifying mRNAs that are up-regulated in prostate cancer (2). Subsequently, TRPM8 expression was also demonstrated to be strongly up-regulated in several other primary tumor types including breast, colon, lung, and skin (2). The following studies identified TRPM8 in a subset of dorsal root and trigeminal neurons (3), and found it to function as a plasma membrane Ca 2ϩ -permeable cation ...

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Menthol and Related Cooling Compounds

Cited by 425 publications

References 75 publications

Chemosensory additivity in trigeminal chemoreception as reflected by detection of mixtures

Chemosensory additivity in trigeminal chemoreception as reflected by detection of mixtures

The lingering question of menthol in cigarettes

TRPM8-independent Menthol-induced Ca2+ Release from Endoplasmic Reticulum and Golgi

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