The Influence of Mecamylamine on Trigeminal and Olfactory Chemoreception of Nicotine

Thuerauf, Norbert; Markovic, Katrin; Braun, G. G.; Bleich, Stefan; Reulbach, Udo; Kornhuber, Johannes; Lunkenheimer, Jens

doi:10.1038/sj.npp.1300842

Cited by 28 publications

(30 citation statements)

References 35 publications

(50 reference statements)

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“…Because nicotine activates capsaicin-sensitive trigeminal neurons (4,7), the contribution of somatosensory input was tested by measuring behavioral responses to nicotine in adult KO animals that had been injected with capsaicin as neonates. This treatment produces systemic and life-long elimination of the majority of capsaicin-sensitive neurons, causing deficits in chemonociceptive reactivity (28).…”

Section: Resultsmentioning

confidence: 99%

Nicotine activates TRPM5-dependent and independent taste pathways

Oliveira‐Maia

Stapleton-Kotloski²,

Lyall

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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The orosensory responses elicited by nicotine are relevant for the development and maintenance of addiction to tobacco products. However, although nicotine is described as bitter tasting, the molecular and neural substrates encoding the taste of nicotine are unclear. Here, rats and mice were used to determine whether nicotine activates peripheral and central taste pathways via TRPM5-dependent mechanisms, which are essential for responses to other bitter tastants such as quinine, and/or via nicotinic acetylcholine receptors (nAChRs). When compared with wild-type mice, Trpm5 ؊/؊ mice had reduced, but not abolished, chorda tympani (CT) responses to nicotine. In both genotypes, lingual application of mecamylamine, a nAChR-antagonist, inhibited CT nerve responses to nicotine and reduced behavioral responses of aversion to this stimulus. In accordance with these findings, rats were shown to discriminate between nicotine and quinine presented at intensity-paired concentrations. Moreover, rat gustatory cortex (GC) neural ensemble activity could also discriminate between these two bitter tastants. Mecamylamine reduced both behavioral and GC neural discrimination between nicotine and quinine. In summary, nicotine elicits taste responses through peripheral TRPM5-dependent pathways, common to other bitter tastants, and nAChR-dependent and TRPM5-independent pathways, thus creating a unique sensory representation that contributes to the sensory experience of tobacco products. chorda tympani ͉ gustatory cortex ͉ neurophysiology ͉ preference ͉ discrimination

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Section: Resultsmentioning

confidence: 99%

Nicotine activates TRPM5-dependent and independent taste pathways

Oliveira‐Maia

Stapleton-Kotloski²,

Lyall

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…By specific we mean processes in which the key step relies on the irritant possessing a narrowly tuned chemical structure, functionality, or conformation that when even slightly modified produces a dramatic change in activity. There are some prototypical irritants, usually active at much lower concentrations than general VOCs, that fit tightly and activate strongly a particular receptor, e.g., nicotine (Alimohammadi and Silver 2000;Thuerauf et al 2006), capsaicin (Bae et al 2004;Silver et al 2006), isothiocyanates and thiosulfinates (Bautista et al 2006), and menthol (Bandell et al 2006), but even these "specific" receptors often display broad chemical selectivity (Trevisani et al 2002;Macpherson et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Concentration-detection functions for eye irritation evoked by homologous n-alcohols and acetates approaching a cut-off point

et al. 2007

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We measured concentration-detection (i.e., psychometric) functions for the eye irritation evoked by three homologous n-alcohols (1-nonanol, 1-decanol, and 1-undecanol) and two homologous acetates (nonyl and decyl acetate). A vapor delivery device based on a dynamic dilution of stimuli in nitrogen served to present various concentrations of each compound, including the undiluted vapor, to the subjects (n≥26).Delivered concentrations were quantified by gas chromatography. Detection probability (P) was assessed via a three-alternative, forced-choice procedure, and quantified on a scale ranging from P = 0.0 (chance detection) to P = 1.0 (perfect detection). Flowrate to the eye equaled 2.5 L/min and time of exposure was 6 sec. The functions for 1-undecanol and decyl acetate plateau at P ≈ 0.5 and P ≈ 0.25, respectively, such that further increases in concentration failed to increase detection notably. Thus, both series reached a break-point, or cut-off, in detection of ocular irritation. The present outcome provides additional evidence that the cut-off does not rest on the low vapor concentration of the homolog but, more likely, on the homolog exceeding a critical molecular dimension(s) which prevents it from interacting effectively with the appropriate receptors.

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“…VOCs that are reactive towards tissue may also produce nociception by damaging cells and producing secondary release of endogenous chemical mediators activating various ion channels, such as acid sensing ion channels (ASIC), purinergic receptor subtype X channels (P2X), and serotonin ionotropic receptors (Rang et al, 1991, Wood and Docherty, 1997, McCleskey and Gold, 1999, Lee et al, 2005. Pharmacological and molecular-biology studies have identified a number of likely chemesthetic receptors such as the nicotine (Thuerauf et al, 1999, Alimohammadi and Silver, 2000, Thuerauf et al, 2006, capsaicin (Walpole et al, 1996), and menthol (Eccles, 1994, Peier et al, 2002 receptors. The last two receptors are also thermoreceptors responding to warm/ hot and cool/cold temperatures, respectively (Caterina et al, 1997, McKemy et al, 2002.…”

Section: Introductionmentioning

confidence: 99%

Cutoff in detection of eye irritation from vapors of homologous carboxylic acids and aliphatic aldehydes

et al. 2007

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Using neat vapors of selected homologous aldehydes (decanal, undecanal, dodecanal) and carboxylic acids (pentanoic, hexanoic, heptanoic, octanoic, nonanoic), we explored the point where a certain homolog (and all larger ones) becomes undetectable by eye irritation (i.e., by ocular chemesthesis). This phenomenon has been observed in other homologous series that also reach a break-point, or cut-off, in chemesthetic detection. Participants (11≤n≤32) were tested using a three-alternative, forced-choice procedure. Flowrate to the eye equaled 4 or 8 L/min and time of exposure was 6 sec. The outcome showed that dodecanal and heptanoic acid were the shortest undetectable homologs. When the vapor concentration of the stimuli was increased by heating the liquid source to 37°C, homologs located before the cut-off point (e.g., hexanoic acid) became readily detected by all subjects, whereas homologs located at the cut off remained largely undetected. In addition, a comparison of calculated values of eye irritation thresholds for aldehydes and acids (from a successful model of ocular chemesthetic potency) with values of saturated vapor concentration at 23 and 37 °C indicated that the vapor concentration of dodecanal and heptanoic acid should have been enough to produce detection. The outcome suggests that the cut-off observed does not result from a low vapor concentration but from limitations in the structure or dimension(s) of the molecules that render them unsuitable to interact effectively with chemesthetic receptors.

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The Influence of Mecamylamine on Trigeminal and Olfactory Chemoreception of Nicotine

Cited by 28 publications

References 35 publications

Nicotine activates TRPM5-dependent and independent taste pathways

Nicotine activates TRPM5-dependent and independent taste pathways

Concentration-detection functions for eye irritation evoked by homologous n-alcohols and acetates approaching a cut-off point

Cutoff in detection of eye irritation from vapors of homologous carboxylic acids and aliphatic aldehydes

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