PMID- 19583705
OWN - NLM
STAT- MEDLINE
DCOM- 20100323
LR  - 20161125
IS  - 1748-1716 (Electronic)
IS  - 1748-1708 (Linking)
VI  - 197
IP  - 3
DP  - 2009 Nov
TI  - Enhanced pulmonary expression of the TrkB neurotrophin receptor in hypoxic rats 
      is associated with increased acetylcholine-induced airway contractility.
PG  - 253-64
LID - 10.1111/j.1748-1716.2009.02016.x [doi]
AB  - 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.
FAU - Sciesielski, L K
AU  - Sciesielski LK
AD  - Institut fur Vegetative Physiologie, Charite- Universitatsmedizin Berlin, Berlin, 
      Germany.
FAU - Paliege, A
AU  - Paliege A
FAU - Martinka, P
AU  - Martinka P
FAU - Scholz, H
AU  - Scholz H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090706
PL  - England
TA  - Acta Physiol (Oxf)
JT  - Acta physiologica (Oxford, England)
JID - 101262545
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Messenger)
RN  - 0 (Vasodilator Agents)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - N9YNS0M02X (Acetylcholine)
SB  - IM
MH  - Acetylcholine/*pharmacology
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Gene Expression
MH  - Hypoxia/*physiopathology
MH  - Immunoblotting
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - Lung/drug effects/metabolism
MH  - Male
MH  - Muscle Contraction/drug effects/physiology
MH  - Muscle, Smooth/drug effects/physiology
MH  - Nitric Oxide/metabolism
MH  - RNA, Messenger/analysis
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, trkB/*biosynthesis
MH  - Respiratory Mucosa/drug effects/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/physiology
MH  - Trachea/drug effects/*metabolism
MH  - Vasodilator Agents/*pharmacology
EDAT- 2009/07/09 09:00
MHDA- 2010/03/24 06:00
CRDT- 2009/07/09 09:00
PHST- 2009/07/09 09:00 [entrez]
PHST- 2009/07/09 09:00 [pubmed]
PHST- 2010/03/24 06:00 [medline]
AID - APS2016 [pii]
AID - 10.1111/j.1748-1716.2009.02016.x [doi]
PST - ppublish
SO  - Acta Physiol (Oxf). 2009 Nov;197(3):253-64. doi: 
      10.1111/j.1748-1716.2009.02016.x. Epub 2009 Jul 6.