Ethanol modulates the VR-1 variant amiloride-insensitive salt taste receptor. II. Effect on chorda tympani salt responses.
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.
Lyall
Vijay
V
Department of Physiology, Division of Nephrology, Virginia Commonwealth University, Richmond, VA 23298, USA. vlyall@hsc.vcu.edu
Heck
Gerard L
GL
Phan
Tam-Hao T
TH
Mummalaneni
Shobha
S
Malik
Shahbaz A
SA
Vinnikova
Anna K
AK
Desimone
John A
JA
D000465:Algorithms; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D016764:Cell Polarity / Q000502:physiology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002814:Chorda Tympani Nerve / Q000187:drug effects*; D002934:Cinnamates / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000235:genetics; D012964:Sodium / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013649:Taste / Q000187:drug effects*; D013652:Taste Threshold / Q000187:drug effects; D013696:Temperature; D014059:Tongue / Q000166:cytology / Q000648:ultrastructure
D000813:Anilides; D002492:Central Nervous System Depressants; D002934:Cinnamates; D004224:Diterpenes; D004232:Diuretics; C477659:N-(3-methoxyphenyl)-4-chlorocinnamanilide; D011955:Receptors, Drug; C013407:benzamil; D000431:Ethanol; D012965:Sodium Chloride; D000584:Amiloride; D012964:Sodium; C024353:resiniferatoxin; C071423:capsazepine; D002211:Capsaicin