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Caffeine Reversal of Opioid-Evoked and Endogenous Inspiratory Depression in Perinatal Rat En Bloc Medullas and Slices

  • Araya Ruangkittisakul
  • Bogdan Panaitescu
  • Junya Kuribayashi
  • Klaus Ballanyi
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 669)

Abstract

Caffeine counters endogenous or drug-evoked depression of breathing in (preterm) infants. Despite its common clinical use, little is known on central nervous mechanisms of its stimulatory respiratory action. We show that millimolar concentrations of caffeine are needed in perinatal rat en bloc medullas and medullary slices for stimulation of fictive inspiratory rhythms that were either endogenously slow in fetuses or depressed by prostagandins or opioids. Findings suggests that caffeine blocks phospodiesterase-4 thus raising cAMP in rhythmogenic pre-Bötzinger complex (preBötC) networks and/or cells driving the inspiratory preBötC.

Keywords

Endogenous Depression Agonist DAMGO Medullary Slice Endogenous Neuromodulator Medullary Respiratory Neuron 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

Supported by CIHR, AHFMR, CFI and ISRIP/ASRA. KB is a AHFMR Scientist. BP and AR have been awarded a CIHR studentship (MFN training grant).

References

  1. Ballanyi, K. (2004) Neuromodulation of the perinatal respiratory network. Curr. Neuropharmacol. 2, 221–243.CrossRefGoogle Scholar
  2. Ballanyi, K., Lalley, P.M., Hoch, B., and Richter, D.W. (1997) cAMP-dependent reversal of opioid- and prostaglandin-mediated depression of the isolated respiratory network in newborn rats. J. Physiol. 504, 127–134.CrossRefPubMedGoogle Scholar
  3. Ballanyi, K., Onimaru, H., and Homma, I. (1999) Respiratory network function in the isolated brainstem-spinal cord of newborn rats. Prog. Neurobiol. 59, 583–634.CrossRefPubMedGoogle Scholar
  4. Ballanyi, K. and Ruangkittisakul, A. (2009) Structure-function analysis of rhythmogenic inspiratory pre-Bötzinger complex networks in “calibrated” newborn rat brainstem slices. Respir. Physiol. Neurobiol. 168, 158–178.CrossRefPubMedGoogle Scholar
  5. Fredholm, B.B., Bättig, K., Holmén, J., Nehlig, A., and Zvartau, E.E. (1999) Actions of caffeine in the brain with special reference to factors that contribute to its wide-spread use. Pharmacol. Rev. 51, 83–133.PubMedGoogle Scholar
  6. Herlenius, E., Adén, U., Tang, L.Q., and Lagercrantz, H. (2002) Perinatal respiratory control and its modulation by adenosine and caffeine in the rat. Pediatr. Res. 51, 4–12.CrossRefPubMedGoogle Scholar
  7. Manzke, T., Guenther, U., Ponimaskin, E.G., Haller, M., Dutschmann, M., Schwarzacher, S., and Richter, D.W. (2003) 5-HT4(a) receptors avert opioid-induced breathing depression without loss of analgesia. Science 301, 226–229.CrossRefPubMedGoogle Scholar
  8. Montandon, G., Kinkead, R., and Bairam, A. (2007) Disruption of adenosinergic modulation of ventilation at rest and during hypercapnia by neonatal caffeine in young rats: Role of adenosine A(1) and A(2A) receptors. Am. J. Physiol. Regul. Integr. Comp. Physiol. 292, R1621–R1631.PubMedGoogle Scholar
  9. Panaitescu, B., Ruangkittisakul, A., and Ballanyi, K. (2009) Silencing by raised extracellular Ca2+ of pre-Bötzinger complex neurons in newborn rat brainstem slices without change of membrane potential or input resistance. Neurosci. Lett. 456, 25–29.CrossRefPubMedGoogle Scholar
  10. Peña, F. and García, O. (2006) Breathing generation and potential pharmacotherapeutic approaches to central respiratory disorders. Curr. Med. Chem. 13, 2681–2693.CrossRefPubMedGoogle Scholar
  11. Richter, D.W., Lalley, P.M., Pierrefiche, O., Haji, A., Bischoff, A.M., Wilken, B., and Hanefeld, V. (1997) Intracellular signal pathways controlling respiratory neurons. Resp. Physiol. 110, 113–123.CrossRefGoogle Scholar
  12. Ruangkittisakul, A., Secchia, L., Bornes, T.D., Palathinkal, D.M., and Ballanyi, K. (2007) Dependence on extracellular Ca2+/K+ antagonism of inspiratory centre rhythms in slices and en bloc preparations of newborn rat brainstem. J. Physiol. 584, 489–508.CrossRefPubMedGoogle Scholar
  13. Ruangkittisakul, A. and Ballanyi, K. (2006) Reversal by phosphodiesterase-4 blockers of in vitro apnea in the isolated brainstem-spinal cord preparation from newborn rats. Neurosci. Lett. 401, 194–198.CrossRefPubMedGoogle Scholar
  14. Ruangkittisakul, A., Schwarzacher, S.W., Secchia, L., Poon, B.Y., Ma, Y., Funk, G.D., and Ballanyi, K. (2006) High sensitivity to neuromodulator-activated signalling pathways at physiological [K+] of confocally-imaged respiratory centre neurons in online-calibrated newborn rat brainstem slices. J. Neurosci. 26, 11870–11880.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Araya Ruangkittisakul
    • 1
  • Bogdan Panaitescu
    • 1
  • Junya Kuribayashi
    • 1
  • Klaus Ballanyi
    • 1
  1. 1.Department of PhysiologyUniversity of AlbertaAlbertaCanada

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