title: A novel pharmacological probe links the amiloride-insensitive NaCl, KCl, and NH(4)Cl chorda tympani taste responses.
abstract: Chorda tympani taste nerve responses to NaCl can be dissected pharmacologically into amiloride-sensitive and -insensitive components. It is now established that the amiloride-sensitive, epithelial sodium channel acts as a sodium-specific ion detector in taste receptor cells (TRCs). Much less is known regarding the cellular origin of the amiloride-insensitive component, but its anion dependence indicates an important role for paracellular shunts in the determination of its magnitude. However, this has not precluded the possibility that undetected apical membrane ion pathways in TRCs may also contribute to its origin. Progress toward making such a determination has suffered from lack of a pharmacological probe for an apical amiloride-insensitive taste pathway. We present data here showing that, depending on the concentration used, cetylpyridinium chloride (CPC) can either enhance or inhibit the amiloride-insensitive response to NaCl. The CPC concentration giving maximal enhancement was 250 microM. At 2 mM, CPC inhibited the entire amiloride-insensitive part of the NaCl response. The NaCl response is, therefore, composed entirely of amiloride- and CPC-sensitive components. The magnitude of the maximally enhanced CPC-sensitive component varied with the NaCl concentration and was half-maximal at [NaCl] = 62 +/- 11 (SE) mM. This was significantly less than the corresponding parameter for the amiloride-sensitive component (268 +/- 71 mM). CPC had similar effects on KCl and NH(4)Cl responses except that in these cases, after inhibition with 2 mM CPC, a significant CPC-insensitive response remained. CPC (2 mM) inhibited intracellular acidification of TRCs due to apically presented NH(4)Cl, suggesting that CPC acts on an apical membrane nonselective cation pathway.
authors.affiliation: Department of Physiology, Virginia Commonwealth University, Richmond, Virginia 23298-0551, USA. jdesimone@hsc.vcu.edu
authors.forename: J A
authors.initials: JA
authors.lastname: DeSimone
authors.forename: V
authors.initials: V
authors.lastname: Lyall
authors.forename: G L
authors.initials: GL
authors.lastname: Heck
authors.forename: T H
authors.initials: TH
authors.lastname: Phan
authors.forename: R I
authors.initials: RI
authors.lastname: Alam
authors.forename: G M
authors.initials: GM
authors.lastname: Feldman
authors.forename: R M
authors.initials: RM
authors.lastname: Buch
mesh_terms: D000584:Amiloride / Q000494:pharmacology*; D000643:Ammonium Chloride / Q000494:pharmacology*; D000818:Animals; D002594:Cetylpyridinium / Q000494:pharmacology; D002814:Chorda Tympani Nerve / Q000187:drug effects* / Q000502:physiology; D004351:Drug Resistance; D006863:Hydrogen-Ion Concentration; D009994:Osmolar Concentration; D011189:Potassium Chloride / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology*; D013649:Taste / Q000187:drug effects* / Q000502:physiology
chemical_list: D000643:Ammonium Chloride; D012965:Sodium Chloride; D011189:Potassium Chloride; D000584:Amiloride; D002594:Cetylpyridinium