title: Role of the ectonucleotidase NTPDase2 in taste bud function.
abstract: Taste buds are unusual in requiring ATP as a transmitter to activate sensory nerve fibers. In response to taste stimuli, taste cells release ATP, activating purinergic receptors containing the P2X2 and P2X3 subunits on taste nerves. In turn, the released ATP is hydrolyzed to ADP by a plasma membrane nucleoside triphosphate previously identified as nucleoside triphosphate diphosphohydrolase-2 (NTPDase2). In this paper we investigate the role of this ectonucleotidase in the function of taste buds by examining gene-targeted Entpd2-null mice globally lacking NTPDase2. RT-PCR confirmed the absence of NTPDase2, and ATPase enzyme histochemistry reveals no reaction product in taste buds of knockout mice, suggesting that NTPDase2 is the dominant form in taste buds. RT-PCR and immunocytochemistry demonstrated that in knockout mice all cell types are present in taste buds, even those cells normally expressing NTPDase2. In addition, the overall number and size of taste buds are normal in Entpd2-null mice. Luciferin/luciferase assays of circumvallate tissue of knockout mice detected elevated levels of extracellular ATP. Electrophysiological recordings from two taste nerves, the chorda tympani and glossopharyngeal, revealed depressed responses to all taste stimuli in Entpd2-null mice. Responses were more depressed in the glossopharyngeal nerve than in the chorda tympani nerve and involved all taste qualities; responses in the chorda tympani were more depressed to sweet and umami stimuli than to other qualities. We suggest that the excessive levels of extracellular ATP in the Entpd2-knockout animals desensitize the P2X receptors associated with nerve fibers, thereby depressing taste responses.
authors: Department of Otolaryngology, University of Colorado Medical School, Aurora, CO 80045, USA.
authors: Aurelie
authors: A
authors: Vandenbeuch
authors: Catherine B
authors: CB
authors: Anderson
authors: Jason
authors: J
authors: Parnes
authors: Keiichi
authors: K
authors: Enjyoji
authors: Simon C
authors: SC
authors: Robson
authors: Thomas E
authors: TE
authors: Finger
authors: Sue C
authors: SC
authors: Kinnamon
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002814:Chorda Tympani Nerve / Q000502:physiology; D015870:Gene Expression; D005930:Glossopharyngeal Nerve / Q000502:physiology; D007150:Immunohistochemistry; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013649:Taste / Q000502:physiology*; D013650:Taste Buds / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology*
chemical_list: D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; C027201:ectoATPase
keywords: E-NTPDase; gustatory; mouse; purinergic signaling; synaptic function
references: Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6436-41
references: 17389364
references: PLoS One. 2012;7(1):e30032
references: 22253866
references: J Physiol. 2007 Oct 15;584(Pt 2):473-88
references: 17702819
references: Chem Senses. 2008 Mar;33(3):243-54
references: 18156604
references: Purinergic Signal. 2006 Jun;2(2):409-30
references: 18404480
references: EMBO J. 2007 Feb 7;26(3):657-67
references: 17235286
references: J Histochem Cytochem. 1992 Dec;40(12):1919-28
references: 1453008
references: J Comp Neurol. 2009 May 10;514(2):131-44
references: 19266560
references: Purinergic Signal. 2005 Jun;1(2):193-204
references: 18404504
references: Nature. 2013 Mar 14;495(7440):223-6
references: 23467090
references: Science. 2005 Dec 2;310(5753):1495-9
references: 16322458
references: J Neurosci. 2011 Sep 21;31(38):13654-61
references: 21940456
references: Histochem Cell Biol. 2004 May;121(5):419-26
references: 15103469
references: J Clin Oncol. 1995 Sep;13(9):2174-86
references: 7666076
references: Neuropharmacology. 2008 Dec;55(7):1212-8
references: 18768143
references: Nature. 2000 Jan 6;403(6765):86-9
references: 10638758
references: Nat Med. 1999 Sep;5(9):1010-7
references: 10470077
references: J Neurosci. 2009 Nov 4;29(44):13909-18
references: 19890001
references: J Pharmacol Exp Ther. 2007 Sep;322(3):1269-77
references: 17565006
references: J Comp Neurol. 1985 May 1;235(1):48-60
references: 3989005
references: Purinergic Signal. 2012 Sep;8(3):437-502
references: 22555564
references: Exp Cell Res. 1967 Jun;46(3):607-8
references: 4283627
references: Nature. 2006 Nov 16;444(7117):288-94
references: 17108952
references: Nature. 2006 Aug 24;442(7105):934-8
references: 16929298
references: J Neurosci. 2012 Jan 4;32(1):322-30
references: 22219293
references: J Comp Neurol. 1997 Feb 17;378(3):389-410
references: 9034899
references: J Neurosci. 1997 Sep 1;17(17):6529-33
references: 9254665
references: Hear Res. 2009 Jul;253(1-2):77-82
references: 19327391
references: Physiol Rev. 2002 Oct;82(4):1013-67
references: 12270951
references: J Cell Biol. 2010 Aug 9;190(3):285-96
references: 20696704
references: J Comp Neurol. 2006 Jul 1;497(1):1-12
references: 16680780
references: J Pharmacol Exp Ther. 2001 Mar;296(3):1043-50
references: 11181939
references: Neuroreport. 1999 Apr 6;10(5):1107-11
references: 10321492
references: J Neurophysiol. 2010 Aug;104(2):896-901
references: 20519578
references: J Comp Neurol. 2001 Nov 5;440(1):97-108
references: 11745610
references: Nature. 2013 Feb 28;494(7438):472-5
references: 23407495
references: J Comp Neurol. 1999 Jun 21;409(1):13-24
references: 10363708
references: Cell Tissue Res. 2006 Mar;323(3):377-82
references: 16328495