PMID- 18305238
OWN - NLM
STAT- MEDLINE
DCOM- 20080408
LR  - 20220309
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 28
IP  - 9
DP  - 2008 Feb 27
TI  - Spinal adenosine A2a receptor activation elicits long-lasting phrenic motor 
      facilitation.
PG  - 2033-42
LID - 10.1523/JNEUROSCI.3570-07.2008 [doi]
AB  - Acute intermittent hypoxia elicits a form of spinal, brain-derived neurotrophic 
      factor (BDNF)-dependent respiratory plasticity known as phrenic long-term 
      facilitation. Ligands that activate G(s)-protein-coupled receptors, such as the 
      adenosine 2a receptor, mimic the effects of neurotrophins in vitro by 
      transactivating their high-affinity receptor tyrosine kinases, the Trk receptors. 
      Thus, we hypothesized that A2a receptor agonists would elicit phrenic long-term 
      facilitation by mimicking the effects of BDNF on TrkB receptors. Here we 
      demonstrate that spinal A2a receptor agonists transactivate TrkB receptors in the 
      rat cervical spinal cord near phrenic motoneurons, thus inducing long-lasting 
      (hours) phrenic motor facilitation. A2a receptor activation increased 
      phosphorylation and new synthesis of an immature TrkB protein, induced TrkB 
      signaling through Akt, and strengthened synaptic pathways to phrenic motoneurons. 
      RNA interference targeting TrkB mRNA demonstrated that new TrkB protein synthesis 
      is necessary for A2a-induced phrenic motor facilitation. A2a receptor activation 
      also increased breathing in unanesthetized rats, and improved breathing in rats 
      with cervical spinal injuries. Thus, small, highly permeable drugs (such as 
      adenosine receptor agonists) that transactivate TrkB receptors may provide an 
      effective therapeutic strategy in the treatment of patients with ventilatory 
      control disorders, such as obstructive sleep apnea, or respiratory insufficiency 
      after spinal injury or during neurodegenerative diseases.
FAU - Golder, Francis J
AU  - Golder FJ
AD  - Department of Comparative Biosciences, University of Wisconsin, Madison, 
      Wisconsin 53706, USA.
FAU - Ranganathan, Lavanya
AU  - Ranganathan L
FAU - Satriotomo, Irawan
AU  - Satriotomo I
FAU - Hoffman, Michael
AU  - Hoffman M
FAU - Lovett-Barr, Mary Rachael
AU  - Lovett-Barr MR
FAU - Watters, Jyoti J
AU  - Watters JJ
FAU - Baker-Herman, Tracy L
AU  - Baker-Herman TL
FAU - Mitchell, Gordon S
AU  - Mitchell GS
LA  - eng
GR  - R01 HL080209/HL/NHLBI NIH HHS/United States
GR  - T32 HL007654/HL/NHLBI NIH HHS/United States
GR  - HL80209/HL/NHLBI NIH HHS/United States
GR  - HL69064/HL/NHLBI NIH HHS/United States
GR  - R01 HL069064/HL/NHLBI NIH HHS/United States
GR  - R37 HL069064/HL/NHLBI NIH HHS/United States
GR  - HL07654/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Adenosine A2 Receptor Antagonists)
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (MSX 3 compound)
RN  - 0 (Phenethylamines)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptor, Adenosine A2A)
RN  - 0 (Xanthines)
RN  - 120225-54-9 (2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - Action Potentials/drug effects/physiology
MH  - Adenosine/analogs & derivatives/pharmacology
MH  - Adenosine A2 Receptor Antagonists
MH  - Animals
MH  - Antihypertensive Agents/pharmacology
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Drug Interactions
MH  - Enzyme-Linked Immunosorbent Assay/methods
MH  - Male
MH  - Motor Neurons/drug effects/*physiology
MH  - Phenethylamines/pharmacology
MH  - Phrenic Nerve/drug effects/*physiology
MH  - Plethysmography/methods
MH  - RNA, Small Interfering/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Adenosine A2A/*metabolism
MH  - Receptor, trkB/genetics/metabolism
MH  - Spinal Cord/drug effects/*metabolism
MH  - Spinal Cord Injuries/metabolism/physiopathology
MH  - Xanthines/pharmacology
PMC - PMC6671860
EDAT- 2008/02/29 09:00
MHDA- 2008/04/09 09:00
PMCR- 2008/08/27
CRDT- 2008/02/29 09:00
PHST- 2008/02/29 09:00 [pubmed]
PHST- 2008/04/09 09:00 [medline]
PHST- 2008/02/29 09:00 [entrez]
PHST- 2008/08/27 00:00 [pmc-release]
AID - 28/9/2033 [pii]
AID - 3320894 [pii]
AID - 10.1523/JNEUROSCI.3570-07.2008 [doi]
PST - ppublish
SO  - J Neurosci. 2008 Feb 27;28(9):2033-42. doi: 10.1523/JNEUROSCI.3570-07.2008.