Ethanol modulates the VR-1 variant amiloride-insensitive salt taste receptor. II. Effect on chorda tympani salt responses

J Gen Physiol. 2005 Jun;125(6):587-600. doi: 10.1085/jgp.200509264.

Abstract

The effect of ethanol on the amiloride- and benzamil (Bz)-insensitive salt taste receptor was investigated by direct measurement of intracellular Na(+) activity ([Na(+)](i)) using fluorescence imaging in polarized fungiform taste receptor cells (TRCs) and by chorda tympani (CT) taste nerve recordings. CT responses to KCl and NaCl were recorded in Sprague-Dawley rats, and in wild-type (WT) and vanilloid receptor-1 (VR-1) knockout mice (KO). CT responses were monitored in the presence of Bz, a specific blocker of the epithelial Na(+) channel (ENaC). CT responses were also recorded in the presence of agonists (resiniferatoxin and elevated temperature) and antagonists (capsazepine and SB-366791) of VR-1 that similarly modulate the Bz-insensitive VR-1 variant salt taste receptor. In the absence of mineral salts, ethanol induced a transient decrease in TRC volume and elicited only transient phasic CT responses. In the presence of mineral salts, ethanol increased the apical cation flux in TRCs without a change in volume, increased transepithelial electrical resistance across the tongue, and elicited CT responses that were similar to salt responses, consisting of both a phasic component and a sustained tonic component. At concentrations <50%, ethanol enhanced responses to KCl and NaCl, while at ethanol concentrations >50%, those CT responses were inhibited. Resiniferatoxin and elevated temperature increased the sensitivity of the CT response to ethanol in salt-containing media, and SB-366791 inhibited the effect of ethanol, resiniferatoxin, and elevated temperature on the CT responses to mineral salts. VR-1 KO mice demonstrated no Bz-insensitive CT response to NaCl and no sensitivity to ethanol. We conclude that ethanol increases salt taste sensitivity by its direct action on the Bz-insensitive VR-1 variant salt taste receptor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Algorithms
  • Amiloride / analogs & derivatives
  • Amiloride / pharmacology
  • Anilides / pharmacology
  • Animals
  • Capsaicin / analogs & derivatives
  • Capsaicin / pharmacology
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cell Polarity / physiology
  • Central Nervous System Depressants / pharmacology*
  • Chorda Tympani Nerve / drug effects*
  • Cinnamates / pharmacology
  • Diterpenes / pharmacology
  • Diuretics / pharmacology
  • Ethanol / pharmacology*
  • Female
  • In Vitro Techniques
  • Mice
  • Mice, Knockout
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Drug / antagonists & inhibitors
  • Receptors, Drug / drug effects*
  • Receptors, Drug / genetics
  • Sodium / metabolism
  • Sodium Chloride / pharmacology*
  • Stimulation, Chemical
  • Taste / drug effects*
  • Taste Threshold / drug effects
  • Temperature
  • Tongue / cytology
  • Tongue / ultrastructure

Substances

  • Anilides
  • Central Nervous System Depressants
  • Cinnamates
  • Diterpenes
  • Diuretics
  • N-(3-methoxyphenyl)-4-chlorocinnamanilide
  • Receptors, Drug
  • benzamil
  • Ethanol
  • Sodium Chloride
  • Amiloride
  • Sodium
  • resiniferatoxin
  • capsazepine
  • Capsaicin