Nicotinic Acetylcholine Receptor (nAChR) Dependent Chorda Tympani Taste Nerve Responses to Nicotine, Ethanol and Acetylcholine.

Zuo Jun Ren,Vijay Lyall,Jie Qian,Clive M Baumgarten,John A Desimone,Shobha Mummalaneni,Yael Abreu-Villaça

doi:10.1371/journal.pone.0127936

Abstract

Nicotine elicits bitter taste by activating TRPM5-dependent and TRPM5-independent but neuronal nAChR-dependent pathways. The nAChRs represent common targets at which acetylcholine, nicotine and ethanol functionally interact in the central nervous system. Here, we investigated if the nAChRs also represent a common pathway through which the bitter taste of nicotine, ethanol and acetylcholine is transduced. To this end, chorda tympani (CT) taste nerve responses were monitored in rats, wild-type mice and TRPM5 knockout (KO) mice following lingual stimulation with nicotine free base, ethanol, and acetylcholine, in the absence and presence of nAChR agonists and antagonists. The nAChR modulators: mecamylamine, dihydro-β-erythroidine, and CP-601932 (a partial agonist of the α3β4* nAChR), inhibited CT responses to nicotine, ethanol, and acetylcholine. CT responses to nicotine and ethanol were also inhibited by topical lingual application of 8-chlorophenylthio (CPT)-cAMP and loading taste cells with [Ca2+]i by topical lingual application of ionomycin + CaCl2. In contrast, CT responses to nicotine were enhanced when TRC [Ca2+]i was reduced by topical lingual application of BAPTA-AM. In patch-clamp experiments, only a subset of isolated rat fungiform taste cells exposed to nicotine responded with an increase in mecamylamine-sensitive inward currents. We conclude that nAChRs expressed in a subset of taste cells serve as common receptors for the detection of the TRPM5-independent bitter taste of nicotine, acetylcholine and ethanol.

Highlights

The results presented here show that chorda tympani (CT) responses to nicotine, ethanol, and acetylcholine are blocked by the nicotinic acetylcholine receptors (nAChRs) modulators: mecamylamine (Mec), dihydro-β-erythroidine (DHβE), and CP-601932 [7]
This suggests that the TRPM5-independent taste responses to nicotine are derived from its interactions with nAChRs in taste receptor cells (TRCs) [13,14,15]
These results suggest that WT and TRPM5 KO mice share the same nAChR distribution, and that this difference represents the nicotine CT response due to its interactions with T2Rs

Summary

Introduction

Neuronal nAChRs, the molecular targets of nicotine that initiate dependence in smokers, may contribute to the abusive properties of alcohol. NAChR-Dependent Ethanol and Nicotine CT Responses dopamine release from the nucleus accumbens [5, 6]. NAChRs represent common targets at which ethanol and nicotine functionally interact in the CNS [8, 12] and in TRCs [13,14,15] and provide an important molecular link between the bitter taste of nicotine and alcohol and their systemic effects of addiction, co-dependence and relapse. Chronic nicotine upregulates midbrain nAChRs which may lead to increased dopaminergic neuron activation by ethanol [17]. The co-morbidity between alcohol and nicotine dependence can be attributed, in part, to common genetic factors [18]

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Conclusion