title: Colitis elicits differential changes in the expression levels of receptor tyrosine kinase TrkA and TrkB in colonic afferent neurons: a possible involvement of axonal transport.
abstract: The role of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in colitis-induced hypersensitivity has been suggested. NGF and BDNF facilitate cellular physiology through binding to receptor tyrosine kinase TrkA and TrkB, respectively. The present study by examining the mRNA and/or protein levels of TrkA and TrkB in the distal colon and in colonic primary afferent neurons in the dorsal root ganglia (DRG) during colitis demonstrated that colitis elicited location-specific changes in the mRNA and protein levels of TrkA and TrkB in colonic primary sensory pathways. In colitis both the TrkA and TrkB protein levels were increased in the L1 and S1 DRGs in a time-dependent manner; however, the level of TrkB mRNA but not TrkA mRNA was increased in these DRGs. Further experiments showed that colitis facilitated a retrograde transport of TrkA protein toward and an anterograde transport of TrkA mRNA away from the DRG, which may contribute to the increased TrkA mRNA level in the distal colon during colitis. Colitis also increased the level of NGF mRNA but not BDNF mRNA in the distal colon. Double staining showed that the expression of TrkA but not TrkB was increased in the specifically labeled colonic afferent neurons in the L1 and S1 DRGs during colitis; this increase in TrkA level was attenuated by pretreatment with resiniferatoxin. These results suggested that colitis-induced primary afferent activation involved retrograde transport of TrkA but not TrkB from the distal colon to primary afferent neurons in DRG.
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Li-Ya
authors.initials: LY
authors.lastname: Qiao
authors.forename: John R
authors.initials: JR
authors.lastname: Grider
mesh_terms: D000578:Amidines; D000818:Animals; D001370:Axonal Transport / Q000187:drug effects / Q000502:physiology*; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D003092:Colitis / Q000188:drug therapy / Q000473:pathology*; D003106:Colon / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism*; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
chemical_list: D000578:Amidines; D019208:Brain-Derived Neurotrophic Factor; D004224:Diterpenes; D012333:RNA, Messenger; C031455:diamidino compound 253-50; D020932:Nerve Growth Factor; C024353:resiniferatoxin; D020917:Receptor, trkA; D020813:Receptor, trkB