BDNF-overexpression regulates the reactivity of small pulmonary arteries to neurokinin A.
Brain-derived neurotrophic factor (BDNF) is a key modulator during the development of jugular and nodose ganglia neurons, which represent the origin of a large proportion of the sensory innervation of the lung. It belongs to the family of neurotrophins, which have been shown to induce the expression of tachykinins. To assess the interactions of BDNF and the tachykinin neurokinin A (NKA) in small pulmonary vessels, BDNF-transgenic mice were examined for tachykinin contents in the airways, heart, trigeminal ganglion and jugular and nodose ganglion complex (JNC) using reverse phase HPLC (rpHPLC) and radioimmunoassay. BDNF-overexpression led to increased NKA levels in the heart and the JNC, whereas only slightly enhanced levels in the trigeminal ganglion were detected. Lower NKA levels were found in the lung. To assess vasoreactivity in small arteries, precision cut lung slices were subjected to videomorphometry and the response to NKA was examined, which showed significantly stronger effects in the BDNF-transgenic mice, while NK-2 receptor mRNA expression, assayed by real-time RT-PCR, was reduced. In conclusion, BDNF-overexpression results in decreased levels of NKA in the lung with subsequently increased NKA-sensitivity of small arteries. These findings point to a modulatory role of neurotrophins in small respiratory vessel tone regulation.
Springer
Jochen
J
Div of Allergy Research, Dept of Pediatric Pneumology and Immunology, Charité, Humboldt University, 13353 Berlin, Germany. jochen.springer@charite.de
Wagner
Sabine
S
Subramamiam
Arun
A
McGregor
Gerald P
GP
Groneberg
David A
DA
Fischer
Axel
A
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005786:Gene Expression Regulation; D008168:Lung / Q000098:blood supply / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism; D015288:Neurokinin A / Q000494:pharmacology / Q000502:physiology*; D009475:Neurons, Afferent / Q000378:metabolism; D009620:Nodose Ganglion / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D018041:Receptors, Neurokinin-2 / Q000096:biosynthesis / Q000235:genetics; D012668:Trigeminal Ganglion / Q000378:metabolism; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D018041:Receptors, Neurokinin-2; D015288:Neurokinin A