Journal
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
Volume 200, Issue -, Pages 80-89Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.resp.2014.06.002
Keywords
Neonate; Apnea; Prematurity; Methylxanthine; Carotid body
Categories
Funding
- CIHR [221514]
- SIDS Calgary
- Alberta Innovates - Health Solutions
- Hotchkiss Brain Institute's Dr. T. Chen Fong Doctoral Scholarship in Neuroscience
- O'Brien Center
- Alberta Children's Hospital Research Institute's CIHR Training Program
- Alberta Innovates [201400252] Funding Source: researchfish
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Methylxanthines like caffeine and theophylline have long been used to treat apnea of prematurity. Despite their success in stimulating neonatal breathing, their mechanism of action remains poorly understood. Methylxanthines can act as both non-specific adenosine receptor antagonists and inhibitors of cAMP-dependent phosphodiesterases, sarcoplasmic/endoplasmic reticulum calcium ATPases or receptor-coupled anion channels, depending on the dose used. Though there is evidence for methylxanthine action at the level of the carotid body, the consensus is that methylxanthines stimulate the respiratory centers of the brainstem. Here we used the in situ neonatal rat working heart-brainstem preparation and the ex vivo neonatal rat carotid body preparation to test the hypothesis that methylxanthines act at the level of the carotid body. We conclude that although the neonatal carotid body has active adenosine receptors, the effects of methylxanthine therapy are likely mediated centrally, predominantly via inhibition of cAMP-dependent phosphodiesterase-4. (C) 2014 Elsevier B.V. All rights reserved.
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