title: TRPM5-dependent amiloride- and benzamil-insensitive NaCl chorda tympani taste nerve response.
abstract: Transient receptor potential (TRP) subfamily M member 5 (TRPM5) cation channel is involved in sensing sweet, bitter, umami, and fat taste stimuli, complex-tasting divalent salts, and temperature-induced changes in sweet taste. To investigate if the amiloride- and benzamil (Bz)-insensitive NaCl chorda tympani (CT) taste nerve response is also regulated in part by TRPM5, CT responses to 100 mM NaCl + 5 μM Bz (NaCl + Bz) were monitored in Sprague-Dawley rats, wild-type (WT) mice, and TRP vanilloid subfamily member 1 (TRPV1) and TRPM5 knockout (KO) mice in the presence of resiniferatoxin (RTX), a TRPV1 agonist. In rats, NaCl + Bz + RTX CT responses were also monitored in the presence of triphenylphosphine oxide, a specific TRPM5 blocker, and capsazepine and N-(3-methoxyphenyl)-4-chlorocinnamid (SB-366791), specific TRPV1 blockers. In rats and WT mice, RTX produced biphasic effects on the NaCl + Bz CT response, enhancing the response at 0.5-1 μM and inhibiting it at >1 μM. The NaCl + Bz + SB-366791 CT response in rats and WT mice and the NaCl + Bz CT response in TRPV1 KO mice were inhibited to baseline level and were RTX-insensitive. In rats, blocking TRPV1 by capsazepine or TRPM5 by triphenylphosphine oxide inhibited the tonic NaCl + Bz CT response and shifted the relationship between RTX concentration and the magnitude of the tonic CT response to higher RTX concentrations. TRPM5 KO mice elicited no constitutive NaCl + Bz tonic CT response. The relationship between RTX concentration and the magnitude of the tonic NaCl + Bz CT response was significantly attenuated and shifted to higher RTX concentrations. The results suggest that pharmacological or genetic alteration of TRPM5 activity modulates the Bz-insensitive NaCl CT response and its modulation by TRPV1 agonists.
authors: Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, VA 23219, USA.
authors: ZuoJun
authors: Z
authors: Ren
authors: Mee-Ra
authors: MR
authors: Rhyu
authors: Tam-Hao T
authors: TH
authors: Phan
authors: Shobha
authors: S
authors: Mummalaneni
authors: Karnam S
authors: KS
authors: Murthy
authors: John R
authors: JR
authors: Grider
authors: John A
authors: JA
authors: DeSimone
authors: Vijay
authors: V
authors: Lyall
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D002814:Chorda Tympani Nerve / Q000187:drug effects* / Q000502:physiology*; D002934:Cinnamates / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009943:Organophosphorus Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism; D050916:TRPV Cation Channels / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D013649:Taste / Q000187:drug effects* / Q000502:physiology
chemical_list: D000813:Anilides; D002934:Cinnamates; D004224:Diterpenes; C477659:N-(3-methoxyphenyl)-4-chlorocinnamanilide; D009943:Organophosphorus Compounds; D050053:TRPM Cation Channels; C571007:TRPM5 protein, rat; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C498617:Trpm5 protein, mouse; C013407:benzamil; D012965:Sodium Chloride; D000584:Amiloride; C024353:resiniferatoxin; C071423:capsazepine; D002211:Capsaicin; C063888:triphenylphosphine oxide
keywords: SB-366791; TRPV1; capsazepine; resiniferatoxin; triphenylphosphine oxide
references: Assay Drug Dev Technol. 2010 Dec;8(6):703-13
references: 21158685
references: J Neurosci. 2011 Jun 8;31(23):8634-42
references: 21653867
references: Physiol Behav. 1998 Mar;63(5):945-9
references: 9618021
references: J Neurophysiol. 2011 Nov;106(5):2606-21
references: 21849614
references: J Neurophysiol. 2013 Feb;109(4):1078-90
references: 23221408
references: Chem Senses. 2013 Feb;38(2):137-45
references: 23118204
references: Science. 1981 Nov 27;214(4524):1039-41
references: 7302576
references: Chem Senses. 2005 Jan;30 Suppl 1:i42-3
references: 15738186
references: Physiol Behav. 2007 Aug 15;91(5):620-31
references: 17490693
references: Nature. 2013 Feb 7;494(7435):95-99
references: 23364694
references: Nature. 2013 Feb 28;494(7438):472-5
references: 23407495
references: Am J Physiol. 1999 Oct;277(4):C800-13
references: 10516110
references: Am J Physiol Regul Integr Comp Physiol. 2007 May;292(5):R1799-809
references: 17234959
references: J Neurophysiol. 2010 Mar;103(3):1337-49
references: 20032236
references: J Neurophysiol. 2012 Dec;108(12):3221-32
references: 22993258
references: J Neurophysiol. 2012 Mar;107(6):1632-48
references: 22205652
references: Chem Senses. 2006 Mar;31(3):253-64
references: 16436689
references: J Neurosci. 2009 Feb 25;29(8):2654-62
references: 19244541
references: J Neurophysiol. 2009 Sep;102(3):1591-605
references: 19553475
references: Nature. 2010 Mar 11;464(7286):297-301
references: 20107438
references: J Dent Res. 2003 May;82(5):393-7
references: 12709508
references: BMC Neurosci. 2008 Jan 02;9:1
references: 18171468
references: J Neurosci. 2007 Jan 3;27(1):35-45
references: 17202470
references: J Neurophysiol. 2007 Sep;98(3):1662-74
references: 17615133
references: Nature. 2005 Dec 15;438(7070):1022-5
references: 16355226
references: Neurosci Res. 2013 Apr;75(4):283-8
references: 23458904
references: Cell. 2003 Feb 7;112(3):293-301
references: 12581520
references: J Gen Physiol. 2005 Jun;125(6):569-85
references: 15928403
references: J Physiol. 2004 Jul 1;558(Pt 1):147-59
references: 15146042
references: Chem Senses. 2008 Sep;33(7):665-80
references: 18603652
references: Am J Physiol Regul Integr Comp Physiol. 2012 Dec;303(11):R1195-205
references: 23054171
references: Neuropharmacology. 2004 Jan;46(1):133-49
references: 14654105
references: Am J Physiol Cell Physiol. 2012 Jan 1;302(1):C210-9
references: 21998136
references: Am J Physiol Cell Physiol. 2001 Sep;281(3):C1005-13
references: 11502578
references: Pflugers Arch. 2007 Aug;454(5):759-76
references: 17468883
references: Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1596-601
references: 19164511
references: BMC Neurosci. 2007 Jul 04;8:49
references: 17610722
references: J Neurophysiol. 2012 Dec;108(12):3206-20
references: 22956787
references: Chem Senses. 1997 Jun;22(3):249-55
references: 9218137
references: Brain Res Mol Brain Res. 2002 Oct 30;107(1):17-22
references: 12414119
references: J Gen Physiol. 2005 Jun;125(6):587-600
references: 15928404