PMID- 18515408
OWN - NLM
STAT- MEDLINE
DCOM- 20080923
LR  - 20211020
IS  - 1040-0605 (Print)
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Linking)
VI  - 295
IP  - 2
DP  - 2008 Aug
TI  - Role of brain-derived neurotrophic factor in hyperoxia-induced enhancement of 
      contractility and impairment of relaxation in lung parenchyma.
PG  - L348-55
LID - 10.1152/ajplung.00067.2008 [doi]
AB  - Prolonged hyperoxic exposure contributes to neonatal lung injury, and airway 
      hyperreactivity is characterized by enhanced contraction and impaired relaxation 
      of airway smooth muscle. Our previous data demonstrate that hyperoxia in rat pups 
      upregulates expression of brain-derived neurotrophic factor (BDNF) mRNA and 
      protein, disrupts NO-cGMP signaling, and impairs cAMP production in airway smooth 
      muscle. We hypothesized that BDNF-tyrosine kinase B (TrkB) signaling plays a 
      functional role in airway hyperreactivity via upregulation of cholinergic 
      mechanisms in hyperoxia-exposed lungs. Five-day-old rat pups were exposed to 
      >or=95% oxygen or room air for 7 days and administered daily tyrosine kinase 
      inhibitor K-252a (50 microg x kg(-1) x day(-1) i.p.) to block BDNF-TrkB signaling 
      or vehicle. Lungs were removed for HPLC measurement of ACh or for in vitro force 
      measurement of lung parenchymal strips. ACh content doubled in hyperoxic compared 
      with room air-exposed lungs. K-252a treatment of hyperoxic pups restored ACh 
      content to room air levels. Hyperoxia increased contraction and impaired 
      relaxation of lung strips in response to incremental electrical field 
      stimulation. K-252a administration to hyperoxic pups reversed this increase in 
      contraction and decrease in relaxation. K-252a or TrkB-Fc was used to block the 
      effect of exogenous BDNF in vitro. Both K-252a and TrkB-Fc blocked the effects of 
      exogenous BDNF. Hyperoxia decreased cAMP and cGMP levels in lung strips, and 
      blockade of BDNF-TrkB signaling restored cAMP but not cGMP to control levels. 
      Therefore, hyperoxia-induced increase in activity of BDNF-TrkB receptor signaling 
      appears to play a critical role in enhancing cholinergically mediated contractile 
      responses of lung parenchyma.
FAU - Sopi, Ramadan B
AU  - Sopi RB
AD  - Deptartment of Pediatrics, Rainbow Babies and Children's Hospital, Case Western 
      Reserve University, 11100 Euclid Ave., Cleveland, OH 44106-6009, USA.
FAU - Martin, Richard J
AU  - Martin RJ
FAU - Haxhiu, Musa A
AU  - Haxhiu MA
FAU - Dreshaj, Ismail A
AU  - Dreshaj IA
FAU - Yao, Qin
AU  - Yao Q
FAU - Jafri, Anjum
AU  - Jafri A
FAU - Zaidi, Syed I A
AU  - Zaidi SI
LA  - eng
GR  - HL-50527/HL/NHLBI NIH HHS/United States
GR  - HL-56470/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080530
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Carbazoles)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Indole Alkaloids)
RN  - 97161-97-2 (staurosporine aglycone)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - H2D2X058MU (Cyclic GMP)
RN  - N9YNS0M02X (Acetylcholine)
SB  - IM
MH  - Acetylcholine/metabolism
MH  - Animals
MH  - Animals, Newborn
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Carbazoles/pharmacology
MH  - Cyclic AMP/metabolism
MH  - Cyclic GMP/metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Hyperoxia/*metabolism/pathology
MH  - Indole Alkaloids/pharmacology
MH  - Lung/*metabolism
MH  - Lung Injury
MH  - *Muscle Relaxation/drug effects
MH  - Muscle, Smooth/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/agonists/antagonists & inhibitors/metabolism
MH  - Signal Transduction/drug effects
PMC - PMC2519841
EDAT- 2008/06/03 09:00
MHDA- 2008/09/24 09:00
PMCR- 2009/08/01
CRDT- 2008/06/03 09:00
PHST- 2008/06/03 09:00 [pubmed]
PHST- 2008/09/24 09:00 [medline]
PHST- 2008/06/03 09:00 [entrez]
PHST- 2009/08/01 00:00 [pmc-release]
AID - 00067.2008 [pii]
AID - LCMP-00067-2008 [pii]
AID - 10.1152/ajplung.00067.2008 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2008 Aug;295(2):L348-55. doi: 
      10.1152/ajplung.00067.2008. Epub 2008 May 30.