title: Nicotinic Acetylcholine Receptor (nAChR) Dependent Chorda Tympani Taste Nerve Responses to Nicotine, Ethanol and Acetylcholine.
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.
authors.affiliation: Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, VA, 23219, United States of America.
authors.forename: Zuo Jun
authors.initials: ZJ
authors.lastname: Ren
authors.affiliation: Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, VA, 23219, United States of America.
authors.forename: Shobha
authors.initials: S
authors.lastname: Mummalaneni
authors.affiliation: Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, VA, 23219, United States of America.
authors.forename: Jie
authors.initials: J
authors.lastname: Qian
authors.affiliation: Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, VA, 23219, United States of America.
authors.forename: Clive M
authors.initials: CM
authors.lastname: Baumgarten
authors.affiliation: Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, VA, 23219, United States of America.
authors.forename: John A
authors.initials: JA
authors.lastname: DeSimone
authors.affiliation: Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, VA, 23219, United States of America.
authors.forename: Vijay
authors.initials: V
authors.lastname: Lyall
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects*; D002814:Chorda Tympani Nerve / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013649:Taste / Q000187:drug effects*
chemical_list: D011978:Receptors, Nicotinic; D000431:Ethanol; D009538:Nicotine; D000109:Acetylcholine