Prolonged exposure to NT-3 attenuates cholinergic nerve-mediated contractions in cultured murine airways.
Chronic airway inflammation may induce subsequent airway hyper-responsiveness (AHR) including pathological alteration of neural activity. Asthmatic airways contain elevated levels of neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) albeit, their effect on neural activity is unclear. This study evaluates the effects of NT-3 and BDNF on nerve mediated airway contractions in vitro. Tracheal segments from BALB/c J mice were cultured for 4 days with NT-3 or BDNF. Responsiveness to electric field stimulation (EFS) was evaluated in organ-bath and innervation patterns were examined by quantitative immunohistochemistry. In cultured segments the EFS-induced contractions were inhibited by tetrodotoxin or atropine. NT-3 reduced the EFS contractions in a concentration-dependent manner whereas BDNF had no effect. The amount of nerve fibers, found in conjunction with the tracheal smooth muscle, was similar in NT-3 treated and control segments. In conclusion, NT-3 attenuates cholinergic nerve-mediated contractions of airway in vitro. Considering the elevated levels of NT-3 found in asthmatic airways, the findings imply a protective role of NT-3 in AHR.
Bachar
Ofir
O
Department of Otorhinolaryngology, Laboratory of Clinical Experimental Allergy Research, Malmö University Hospital, SE-20502 Malmö, Sweden. Ofir.Bachar@oron.mas.lu.se
Adner
Mikael
M
Uddman
Rolf
R
Cardell
Lars-Olaf
LO
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D020933:Neurotrophin 3 / Q000494:pharmacology*; D009924:Organ Culture Techniques; D013997:Time Factors; D014132:Trachea / Q000187:drug effects* / Q000294:innervation
D019208:Brain-Derived Neurotrophic Factor; D020933:Neurotrophin 3; D000109:Acetylcholine