title: TRPV1 and TRPA1 function and modulation are target tissue dependent.
abstract: The nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) families of growth factors regulate the sensitivity of sensory neurons. The ion channels transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential channel, subfamily A, member 1 (TRPA1), are necessary for development of inflammatory hypersensitivity and are functionally potentiated by growth factors. We have shown previously that inflamed skin exhibits rapid increases in artemin mRNA with slower, smaller increases in NGF mRNA. Here, using mice, we show that, in inflamed colon, mRNA for both growth factors increased with a pattern distinct from that seen in skin. Differences were also seen in the pattern of TRPV1 and TRPA1 mRNA expression in DRG innervating inflamed skin and colon. Growth factors potentiated capsaicin (a specific TRPV1 agonist) and mustard oil (a specific TRPA1 agonist) behavioral responses in vivo, raising the question as to how these growth factors affect individual afferents. Because individual tissues are innervated by afferents with unique properties, we investigated modulation of TRPV1 and TRPA1 in identified afferents projecting to muscle, skin, and colon. Muscle and colon afferents are twice as likely as skin afferents to express functional TRPV1 and TRPA1. TRPV1 and TRPA1 responses were potentiated by growth factors in all afferent types, but compared with skin afferents, muscle afferents were twice as likely to exhibit NGF-induced potentiation and one-half as likely to exhibit artemin-induced potentiation of TRPV1. Furthermore, skin afferents showed no GDNF-induced potentiation of TRPA1, but 43% of muscle and 38% of colon afferents exhibited GDNF-induced potentiation. These results show that interpretation of afferent homeostatic mechanisms must incorporate properties that are specific to the target tissue.
authors.affiliation: Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Sacha
authors.initials: S
authors.lastname: Malin
authors.forename: Derek
authors.initials: D
authors.lastname: Molliver
authors.forename: Julie A
authors.initials: JA
authors.lastname: Christianson
authors.forename: Erica S
authors.initials: ES
authors.lastname: Schwartz
authors.forename: Pam
authors.initials: P
authors.lastname: Cornuet
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Albers
authors.forename: Brian M
authors.initials: BM
authors.lastname: Davis
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002772:Cholera Toxin / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism; D003106:Colon / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003872:Dermatitis / Q000209:etiology / Q000378:metabolism; D004195:Disease Models, Animal; D005456:Fluorescent Dyes / Q000378:metabolism; D005620:Freund's Adjuvant / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009132:Muscles / Q000378:metabolism; D009434:Neural Pathways / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels / Q000502:physiology*; D013997:Time Factors; D050051:Transient Receptor Potential Channels / Q000378:metabolism*; D014909:Wheat Germ Agglutinins / Q000378:metabolism
chemical_list: D016207:Cytokines; D005456:Fluorescent Dyes; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D014909:Wheat Germ Agglutinins; D005620:Freund's Adjuvant; D002772:Cholera Toxin; D009195:Peroxidase; D002118:Calcium