Abstract
Nicotine evokes chorda tympani (CT) taste nerve responses and an aversive behavior in Trpm5 knockout (KO) mice. The agonists and antagonists of nicotinic acetylcholine receptors (nAChRs) modulate neural and behavioral responses to nicotine in wildtype (WT) mice, Trpm5 KO mice and rats. This indicates that nicotine evokes bitter taste by activating a Trpm5-dependent pathway and a Trpm5-independent but nAChR-dependent pathway. Rat CT responses to ethanol are also partially inhibited by nAChR blockers, mecamylamine and dihydro-β-erythroidine. This indicates that a component of the bitter taste of ethanol is also nAChR-dependent. However, at present the expression and localization of nAChR subunits has not been investigated in detail in taste receptor cells (TRCs). To this end, in situ hybridization, immunohistochemistry and q-RT-PCR techniques were utilized to localize nAChR subunits in fungiform and circumvallate TRCs in WT mice, Trpm5-GFP transgenic mice, nAChR KO mice, and rats. The expression of mRNAs for α7, β2 and β4 nAChR subunits was observed in a subset of rat and WT mouse circumvallate and fungiform TRCs. Specific α3, α4, α7, β2, and β4 antibodies localized to a subset of WT mouse circumvallate and fungiform TRCs. In Trpm5-GFP mice α3, α4, α7, and β4 antibody binding was observed in a subset of Trpm5-positive circumvallate TRCs. Giving nicotine (100 μg/ml) in drinking water to WT mice for 3 weeks differentially increased the expression of α3, α4, α5, α6, α7, β2 and β4 mRNAs in circumvallate TRCs to varying degrees. Giving ethanol (5%) in drinking water to WT mice induced an increase in the expression of α5 and β4 mRNAs in circumvallate TRCs with a significant decrease in the expression of α3, α6 and β2 mRNAs. We conclude that nAChR subunits are expressed in Trpm5-positive TRCs and their expression levels are differentially altered by chronic oral exposure to nicotine and ethanol.
Highlights
We have demonstrated that protein kinase A (PKA) and protein kinase C (PKC) modulators that regulate the activity of nicotinic acetylcholine receptors (nAChRs) [5,6,7] regulate chorda tympani (CT) responses to Nic and ETOH [3]
The expression of α and β nAChR subunit mRNAs was investigated in CV and FF taste papillae sections of mouse tongue using in situ hybridization (ISH) technique
Neurons that expressed α4 nAChR mRNA expressed the β2 nAChR mRNA (S1 Fig; P2), and neurons that expressed α7 nAChR mRNA expressed the β2 nAChR mRNA (S1 Fig; P3). These results demonstrate the validity of our ISH technique for detecting the presence of nAChRs in brain slices and taste tissue
Summary
We observed that both in WT mice and in Trpm KO mice mecamylamine (Mec), a broad spectrum blocker of nAChRs, decreased the magnitude of the CT response to Nic and its aversiveness [2] These studies led us to conclude that unlike quinine, Nic can transduce bitter taste by interacting with two independent but parallel receptor-mediated pathways. In addition to the classical sweet, bitter, umami, salty and sour taste receptors, nAChRs expressed in central and peripheral organs play a major role in the regulation of appetite and body weight [15], and in the neurobiological effects of ETOH [16] In line with these observation, alterations in CT responses to Nic and ETOH by nAChR agonists and antagonists suggest that DHβE-sensitive nAChRs composed of α4β2 and CP-601932-sensitive nAChRs composed of α3β4Ã subunits are most likely involved in Nic- and ETOH-induced increase in the CT response. Our results demonstrate that nAChR mRNA expression levels are differentially altered by chronic oral exposure to nicotine and ethanol
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
