Nicotine activates TRPM5-dependent and independent taste pathways

Abstract

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

TRPM5-dependent amiloride- and benzamil-insensitive NaCl chorda tympani taste nerve response

“…We recorded CT responses to 10 and 20 mM quinine in WT and TRPM5 KO mice. As expected (36), the WT mice responded with a concentrationdependent increase in the CT response to 10 and 20 mM quinine (Fig. 5A).…”

Dysfunctional Chemosensation in Myasthenia Gravis

“…43 Nicotine activates the chorda tympani nerve, a peripheral division of the facial nerve that innervates the taste buds of the anterior tongue. 44 More research is needed, however, to determine whether reports of taste dysfunction reflect true alterations in the ability to detect sweet, sour, bitter, salty, or umami (savory) taste bud-mediated sensations or flavor sensations secondary to olfactory dysfunction. It must be remembered that most food flavors depend on retronasal stimulation of the sense of smell.…”

Validity of early indirect models of taste active sites and advances in new taste technologies enabled by improved models

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