title: Inhibition of TRPA1 channel activity in sensory neurons by the glial cell line-derived neurotrophic factor family member, artemin.
abstract: BACKGROUND
  The transient receptor potential (TRP) channel subtype A1 (TRPA1) is known to be expressed on sensory neurons and respond to changes in temperature, pH and local application of certain noxious chemicals such as allyl isothiocyanate (AITC). Artemin is a neuronal survival and differentiation factor and belongs to the glial cell line-derived neurotrophic factor (GDNF) family. Both TRPA1 and artemin have been reported to be involved in pathological pain initiation and maintenance. In the present study, using whole-cell patch clamp recording technique, in situ hybridization and behavioral analyses, we examined the functional interaction between TRPA1 and artemin.
  
  
  RESULTS
  We found that 85.8 ± 1.9% of TRPA1-expressing neurons also expressed GDNF family receptor alpha 3 (GFR α3), and 87.5 ± 4.1% of GFRα3-expressing neurons were TRPA1-positive. In whole-cell patch clamp analysis, a short-term treatment of 100 ng/ml artemin significantly suppressed the AITC-induced TRPA1 currents. A concentration-response curve of AITC resulting from the effect of artemin showed that this inhibition did not change EC50 but did lower the AITC-induced maximum response. In addition, pre-treatment of artemin significantly suppressed the number of paw lifts induced by intraplantar injection of AITC, as well as the formalin-induced pain behaviors.
  
  
  CONCLUSIONS
  These findings that a short-term application of artemin inhibits the TRPA1 channel's activity and the sequential pain behaviors suggest a role of artemin in regulation of sensory neurons.
authors: Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe, Hyogo 650-8530, Japan.
authors: Naoki
authors: N
authors: Yoshida
authors: Kimiko
authors: K
authors: Kobayashi
authors: Lina
authors: L
authors: Yu
authors: Shenglan
authors: S
authors: Wang
authors: Rengaowa
authors: R
authors: Na
authors: Satoshi
authors: S
authors: Yamamoto
authors: Koichi
authors: K
authors: Noguchi
authors: Yi
authors: Y
authors: Dai
references: Pain. 1992 Oct;51(1):5-17
references: 1454405
references: Brain. 2008 May;131(Pt 5):1241-51
references: 18356188
references: Auton Neurosci. 2004 May 31;112(1-2):1-14
references: 15233925
references: J Biol Chem. 2008 Nov 21;283(47):32691-703
references: 18775987
references: J Neurosci. 2005 Apr 20;25(16):4052-61
references: 15843607
references: Handb Exp Pharmacol. 2007;(179):541-57
references: 17217078
references: Nature. 2007 Feb 1;445(7127):541-5
references: 17237762
references: J Neurosci. 2010 Sep 29;30(39):12958-63
references: 20881114
references: J Physiol. 2007 Aug 15;583(Pt 1):175-93
references: 17584831
references: J Neurosci. 2004 May 5;24(18):4293-9
references: 15128843
references: J Comp Neurol. 2005 Dec 26;493(4):596-606
references: 16304633
references: Cell. 2006 Mar 24;124(6):1269-82
references: 16564016
references: Nat Med. 2003 Nov;9(11):1383-9
references: 14528299
references: Exp Neurol. 1999 Aug;158(2):504-28
references: 10415156
references: J Clin Invest. 2008 Dec;118(12):4049-57
references: 19033673
references: Cell. 2003 Mar 21;112(6):819-29
references: 12654248
references: Curr Biol. 2005 May 24;15(10):929-34
references: 15916949
references: Psychopharmacology (Berl). 1991;104(1):35-44
references: 1882002
references: Brain Res. 2008 Sep 16;1230:80-90
references: 18652806
references: Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12480-5
references: 14523239
references: Novartis Found Symp. 2004;261:4-12; discussion 12-8, 47-54
references: 15469041
references: J Neurosci. 2006 Aug 16;26(33):8578-87
references: 16914684
references: Br J Pharmacol. 2007 May;151(1):153-60
references: 17351650
references: Neuron. 1998 Dec;21(6):1291-302
references: 9883723
references: Neuron. 2004 Mar 25;41(6):849-57
references: 15046718
references: J Peripher Nerv Syst. 2006 Dec;11(4):330-45
references: 17117942
references: Neuron. 2006 Apr 20;50(2):277-89
references: 16630838
references: J Neurosci. 2006 Aug 16;26(33):8588-99
references: 16914685
references: Proc Natl Acad Sci U S A. 2006 Dec 19;103(51):19564-8
references: 17164327
references: Nat Neurosci. 2008 Apr;11(4):488-96
references: 18344995
references: Nature. 2004 Jan 15;427(6971):260-5
references: 14712238
references: Neuron. 2009 Nov 25;64(4):498-509
references: 19945392
references: Eur J Neurosci. 2001 Jun;13(11):2177-82
references: 11422460
references: Eur J Neurosci. 2005 May;21(9):2467-74
references: 15932604
references: J Clin Invest. 2007 Jul;117(7):1979-87
references: 17571167
references: Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13519-24
references: 17684094
references: J Mol Histol. 2006 Jan;37(1-2):69-77
references: 16773224
references: J Biol Chem. 1999 Mar 12;274(11):7325-33
references: 10066796
references: Toxicol Pathol. 2004 May-Jun;32(3):275-94
references: 15204970
references: Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13525-30
references: 17686976