title: Role of voltage gated Ca2+ channels in rat visceral hypersensitivity change induced by 2,4,6-trinitrobenzene sulfonic acid.
abstract: BACKGROUND
  Visceral pain is common symptom involved in many gastrointestinal disorders such as inflammatory bowel disease. The underlying molecular mechanisms remain elusive. We investigated the molecular mechanisms and the role for voltage gated calcium channel (VGCC) in the pathogenesis in a rat model of 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced visceral inflammatory hypersensitivity.
  
  
  RESULTS
  Using Agilent cDNA arrays, we found 172 genes changed significantly in dorsal root ganglia (DRG) of TNBS treated rats. Among these changed genes, Cav1.2 and Cav2.3 were significantly up-regulated. Then the RT-PCR and Western blot further confirmed the up-regulation of Cav1.2 and Cav2.3. The whole cell patch clamp recording of acutely dissociated colonic specific DRG neurons showed that the peak IBa density was significantly increased in colonic neurons of TNBS treated rats compared with control rats (-127.82 ± 20.82 pA/pF Vs -91.67 ± 19.02 pA/pF, n = 9, *P < 0.05). To distinguish the different type of calcium currents with the corresponding selective channel blockers, we found that L-type (-38.56 ± 3.97 pA/pF Vs -25.75 ± 3.35 pA/pF, n = 9, * P < 0.05) and R-type (-13.31 ± 1.36 pA/pF Vs -8.60 ± 1.25 pA/pF, n = 9, * P < 0.05) calcium current density were significantly increased in colonic DRG neurons of TNBS treated rats compared with control rats. In addition, pharmacological blockade with L-type antagonist (nimodipine) and R-type antagonist (SNX-482) with intrathecal injection attenuates visceral pain in TNBS induced inflammatory visceral hypersensitivity.
  
  
  CONCLUSIONS
  Cav1.2 and Cav2.3 in colonic primary sensory neurons play an important role in visceral inflammatory hyperalgesia, which maybe the potential therapeutic targets.
authors.affiliation: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Qian
authors.forename: Dandan
authors.initials: D
authors.lastname: Song
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Xinqiu
authors.initials: X
authors.lastname: Liu
authors.forename: Dong
authors.initials: D
authors.lastname: Tang
authors.forename: Weiyan
authors.initials: W
authors.lastname: Yao
authors.forename: Yaozong
authors.initials: Y
authors.lastname: Yuan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D020908:Calcium Channels, R-Type / Q000235:genetics / Q000378:metabolism*; D002232:Carbocyanines / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D006967:Hypersensitivity / Q000235:genetics / Q000473:pathology*; D007278:Injections, Spinal; D008297:Male; D009553:Nimodipine / Q000008:administration & dosage / Q000494:pharmacology; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013111:Spider Venoms / Q000008:administration & dosage / Q000494:pharmacology; D014302:Trinitrobenzenesulfonic Acid; D014781:Viscera / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
chemical_list: C498917:Cacna1e protein, rat; D020746:Calcium Channels, L-Type; D020908:Calcium Channels, R-Type; D002232:Carbocyanines; D027682:Cation Transport Proteins; C419385:L-type calcium channel alpha(1C); D021122:Protein Subunits; C115521:SNX 482; D013111:Spider Venoms; C024286:3,3'-dioctadecylindocarbocyanine; D009553:Nimodipine; D014302:Trinitrobenzenesulfonic Acid
references.citation: J Biol Chem. 2003 Aug 15;278(33):30732-40
references.pmid: 12796490
references.citation: Pain. 1997 Jan;69(1-2):93-100
references.pmid: 9060018
references.citation: Am J Gastroenterol. 2009 Aug;104(8):2014-27
references.pmid: 19491827
references.citation: Pain. 1998 Jun;76(3):349-355
references.pmid: 9718253
references.citation: Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10465-70
references.pmid: 8816824
references.citation: Eur J Pharmacol. 1998 Jan 26;342(2-3):339-45
references.pmid: 9548406
references.citation: Neuron. 2004 Jan 8;41(1):127-38
references.pmid: 14715140
references.citation: J Physiol. 1998 Nov 15;513 ( Pt 1):55-69
references.pmid: 9782159
references.citation: J Pharmacol Exp Ther. 1997 Sep;282(3):1242-6
references.pmid: 9316831
references.citation: Eur J Pharmacol. 1992 Jul 7;217(2-3):137-41
references.pmid: 1425934
references.citation: Pain. 2005 Apr;114(3):386-396
references.pmid: 15777864
references.citation: Pain. 1995 Jan;60(1):83-90
references.pmid: 7715945
references.citation: J Neurosci. 1994 Aug;14(8):4882-90
references.pmid: 8046458
references.citation: J Neurophysiol. 2001 Jan;85(1):362-73
references.pmid: 11152736
references.citation: Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16773-8
references.pmid: 18946042
references.citation: Brain Res. 2001 Jun 8;903(1-2):231-6
references.pmid: 11382408
references.citation: Biophys J. 2001 Jul;81(1):79-88
references.pmid: 11423396
references.citation: J Neurosci. 2004 Jun 16;24(24):5623-31
references.pmid: 15201335
references.citation: Neurosci Lett. 1996 Mar 1;205(3):161-4
references.pmid: 8852583
references.citation: Pol J Vet Sci. 2007;10(4):263-9
references.pmid: 18198542
references.citation: Neuron. 2003 Jul 31;39(3):483-96
references.pmid: 12895422
references.citation: J Immunol. 2002 Jun 15;168(12):6436-45
references.pmid: 12055263
references.citation: Eur J Neurosci. 2007 Jun;25(12):3561-9
references.pmid: 17610575
references.citation: Neuropharmacology. 1996 Jan;35(1):99-110
references.pmid: 8684602
references.citation: Cell Calcium. 2005 May;37(5):433-42
references.pmid: 15820391
references.citation: Science. 1987 Jan 2;235(4784):46-52
references.pmid: 2432656
references.citation: J Neurosci. 2001 Sep 1;21(17):6694-705
references.pmid: 11517259
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9864-9
references.pmid: 17525149
references.citation: J Neurosci. 2003 Apr 1;23(7):3028-38
references.pmid: 12684490
references.citation: Res Vet Sci. 2009 Apr;86(2):285-92
references.pmid: 18774578
references.citation: Eur Spine J. 2006 Oct;15(10):1529-37
references.pmid: 16474945
references.citation: Brain Res. 1998 Mar 30;788(1-2):20-4
references.pmid: 9554939
references.citation: Neurosci Lett. 2001 Jan 12;297(2):65-8
references.pmid: 11121871
references.citation: Brain Res. 2005 Aug 2;1052(1):63-70
references.pmid: 16005856
references.citation: Spine (Phila Pa 1976). 2003 May 15;28(10):967-72
references.pmid: 12768133
references.citation: Res Vet Sci. 2011 Apr;90(2):291-7
references.pmid: 20630549
references.citation: Brain Res Mol Brain Res. 2001 Nov 30;96(1-2):151-6
references.pmid: 11731020