Effect of nicotine on chorda tympani responses to salty and sour stimuli.
The effect of nicotine on the benzamil (Bz)-insensitive (transient receptor potential vanilloid-1 variant cation channel, TRPV1t) and the Bz-sensitive (epithelial Na(+) channel, ENaC) salt taste receptors and sour taste was investigated by monitoring intracellular Na(+) and H(+) activity (pH(i)) in polarized fungiform taste receptor cells (TRCs) and the chorda tympani (CT) nerve responses to NaCl, KCl, and HCl. CT responses in Sprague-Dawley rats and both wildtype and TRPV1 knockout (KO) mice were recorded in the presence and absence of agonists [resiniferatoxin (RTX) and elevated temperature] and an antagonist (SB-366791) of TRPV1t, the ENaC blocker (Bz), and varying apical pH (pH(o)). At concentrations <0.015 M, nicotine enhanced and at >0.015 M, it inhibited CT responses to KCl and NaCl. Nicotine produced maximum enhancement in the Bz-insensitive NaCl CT response at pH(o) between 6 and 7. RTX and elevated temperature increased the sensitivity of the CT response to nicotine in salt-containing media, and SB-366791 inhibited these effects. TRPV1 KO mice demonstrated no Bz-insensitive CT response to NaCl and no sensitivity to nicotine, RTX, and elevated temperature. We conclude that nicotine modulates salt responses by direct interaction with TRPV1t. At pH(o) >8, the apical membrane permeability of nicotine was increased significantly, resulting in increase in TRC pH(i) and volume, activation of ENaC, and enhancement of the Bz-sensitive NaCl CT response. At pH(o) >8, nicotine also inhibited the phasic component of the HCl CT response. We conclude that the effects of nicotine on ENaC and the phasic HCl CT response arise from increases in TRC pH(i) and volume.
Lyall
Vijay
V
Department of Physiology, Virginia Commonwealth University, Sanger Hall 3010, 1101 E. Marshall St., Richmond, VA 23298-0551, USA. vlyall@vcu.edu
Phan
Tam-Hao T
TH
Mummalaneni
Shobha
S
Mansouri
Mahdis
M
Heck
Gerard L
GL
Kobal
Gerd
G
DeSimone
John A
JA
D000818:Animals; D002814:Chorda Tympani Nerve / Q000187:drug effects / Q000502:physiology*; D053503:Epithelial Sodium Channels / Q000187:drug effects / Q000502:physiology; D005452:Fluoresceins; D006863:Hydrogen-Ion Concentration; D009538:Nicotine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D012965:Sodium Chloride; D050916:TRPV Cation Channels / Q000187:drug effects / Q000502:physiology; D013649:Taste / Q000187:drug effects / Q000502:physiology*
D053503:Epithelial Sodium Channels; D005452:Fluoresceins; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D012965:Sodium Chloride; D011189:Potassium Chloride; D009538:Nicotine; C043829:2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein