dc.contributor.author
Sciesielski, Lina K.
dc.contributor.author
Paliege, Alexander
dc.contributor.author
Martinka, Peter
dc.contributor.author
Scholz, Holger
dc.date.accessioned
2022-12-14T11:52:22Z
dc.date.available
2022-12-14T11:52:22Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/37012
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-36725
dc.description.abstract
AIM
We have recently reported that hypoxia stimulates transcription of the TrkB neurotrophin receptor in cultured cells via stabilization of hypoxia-inducible factor-1alpha. Here we investigated whether the expression of TrkB and other neurotrophin receptors is oxygen-sensitive also in vivo, and explored the functional consequences of an oxygen-regulated TrkB expression.
METHODS
Rats were exposed either to 21% O(2) or 8% O(2) for 6 h and TrkB was analysed by reverse transcription real-time PCR, in situ mRNA hybridization, and immunological techniques. The importance of the brain-derived neurotrophic factor (BDNF)-TrkB pathway in the control of mechanical airway function was assessed on isolated tracheal segments from normoxic and hypoxic rats.
RESULTS
TrkB transcripts were increased approx. 15-fold in the lungs of hypoxic rats, and the respiratory epithelium was identified as the site of enhanced TrkB expression in hypoxia. The TrkB ligand, BDNF, significantly increased the contractile response to acetylcholine (ACh) of isolated tracheal segments from hypoxic but not from normoxic rats. This effect of BDNF was prevented by pre-incubation of the tissue specimens with the tyrosine kinase inhibitor K252a and by mechanical removal of the TrkB containing airway epithelium. Likewise, the nitric oxide (NO) synthase inhibitor l-NAME abrogated the influence of BDNF on ACh-induced contractions of isolated tracheal segments from hypoxic rats.
CONCLUSION
These results demonstrate that systemic hypoxia stimulates expression of the TrkB neurotrophin receptor in the airway epithelium. Furthermore, activation of TrkB signalling by BDNF in hypoxia enhances mechanical airway contractility to ACh through a mechanism that requires NO.
en
dc.rights.uri
http://www.fu-berlin.de/sites/refubium/rechtliches/Nutzungsbedingungen
dc.subject
acetylcholine
en
dc.subject
airway contractility
en
dc.subject
brain-derived neurotrophic factor
en
dc.subject
in situ mRNA hybridization
en
dc.subject
neurotrophin receptors
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Enhanced pulmonary expression of the TrkB neurotrophin receptor in hypoxic rats is associated with increased acetylcholine-induced airway contractility
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.doi
10.1111/j.1748-1716.2009.02016.x
dcterms.bibliographicCitation.journaltitle
Acta Physiologica
dcterms.bibliographicCitation.number
3
dcterms.bibliographicCitation.originalpublishername
Wiley
dcterms.bibliographicCitation.pagestart
253
dcterms.bibliographicCitation.pageend
264
dcterms.bibliographicCitation.volume
197
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.note.author
Original article first published: 2009-10-07.
en
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
19583705
dcterms.isPartOf.eissn
1748-1716