Prolonged exposure to NT-3 attenuates cholinergic nerve-mediated contractions in cultured murine airways

Abstract

Prolonged exposure to NT-3 attenuates cholinergic nerve-mediated contractions in cultured murine airways.Bachar, Ofir; Adner, Mikael; Uddman, Rolf; Cardell, Lars-Olaf General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal AbstractChronic airway inflammation may induce subsequent airway hyperresponsiveness (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 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.

Neurotrophin effects on intracellular Ca2+and force in airway smooth muscle

“…Furthermore, mice and human airways may differ in neurotrophin effects. On the other hand, our data with NT3 in human ASM are consistent with those of Bachar et al (2) on NT3 decrement of force in mouse trachea.…”

“…*Significant difference from control (P Ͻ 0.05). that prolonged NT3 exposure of mouse trachea diminished the responsiveness to electric field stimulation in vitro (2). The findings in our study of BDNF, NT3, and NT4 expression suggest that, even under normal conditions, ASM-derived neurotrophins may have an autocrine or paracrine effect; however, trkB and trkC expression may also allow ASM to react to neurotrophins derived from other sources such as neurons or immune cells.…”

Neurally Mediated Airway Constriction in Human and Other Species: A Comparative Study Using Precision-Cut Lung Slices (PCLS)

“…However, EFS elicited contractions in tracheal preparations of mice in previous studies [32], and in line with that we observed neurally evoked bronchoconstriction in murine PCLS at higher electric fields (figure 2). In sheep PCLS, on the other hand, airways were highly excitable (figures 1, 3) and nerve activation was observed already at low frequencies or even after one single electrical stimulus (0.4 Hz at train width 2.5 s).…”

Nicotine Exaggerates LPS-Induced Airway Hyperreactivity via JNK-Mediated Up-regulation of Toll-Like Receptor 4

“…Electric field stimulation (EFS) was used to access nerve-induced contractions, and carried out according to previous protocols (Bachar et al, 2005a). Tracheal segments were stimulated with EFS by two electrodes placed at opposite sides of the tracheal segments (Current Stimulator Model CS200, J.P. Trading, Aarhus, Denmark).…”