Phrenic Nerve Response to Glutamate Antagonist Microinjection in the Ventral Medulla

  • John L. Beagle
  • Bernard Hoop
  • Homayoun Kazemi
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 450)

Abstract

Effects of amino acid neurotransmitters on central respiratory drive roughly parallel their excitation or inhibition of neurons1. The major amino acid neurotransmitter glutamic acid is of particular interest because it stimulates ventilatory drive centrally at sites and via mechanisms within the surface of the ventral medulla (VM). Glutamate metabolism in the brain is directly related to CO2 metabolism and fixation in the brain. Decarboxylation of glutamate via the enzyme glutamic acid decarboxylase (GAD) localized substantially in nerve endings, results in formation of the inhibitory amino acid and central respiratory depressant, γ-aminobutyric acid (GABA)4. Recent studies5,6 have shown that the classic biphasic ventilatory response to acute hypoxia has a glutamatergic component, namely, the initial hyperventilatory response is mediated in part by central glutamate. Topical application of glutamatergic receptor antagonists during normoxia to the surface of the VM diminishes central ventilatory drive via reduction in phrenic nerve output11. The present study was therefore undertaken with multiple microinjections of the selective noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 to localize in the VM the effects of blocking glutamate receptor on phrenic nerve output and to quantitate the effects via a model of chemoreceptor-antagonist interaction.

Keywords

Phrenic Nerve Binding Rate Anterior Inferior Cerebellar Artery Amino Acid Neurotransmitter Apparent Binding Constant 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bianchi, A. L., M. Denavit-Saubie, and J. Champagnat. Central control of breathing in mammals: neuronal circuitry, membrane properties, and neurotransmitters. Physiol. Rev. 75:1–45, 1995.PubMedGoogle Scholar
  2. 2.
    Chiang, C. H., P. Pappagianopolous, B. Hoop, and H. Kazemi. Central cardiorespiratory effects of glutamate in dogs. J. Appl. Physiol. 60:2056–62, 1986PubMedGoogle Scholar
  3. 3.
    Hoop, B., M. R. Masjedi, V. E. Shih, and H. Kazemi. Brain glutamate metabolism during hypoxia and peripheral chemodenervation. J. Appl. Physiol. 69:147–54, 1990.PubMedGoogle Scholar
  4. 4.
    Kazemi, H., and B. Hoop. Glutamic acid and y-aminobutyric acid neurotransmitters in central control of breathing. J. Appl. Physiol. 70:1–7, 1991.PubMedCrossRefGoogle Scholar
  5. 5.
    Kazemi, H., J. L. Beagle, T. Maher, and B. Hoop. Afferent input from peripheral chemoreceptors in response to hypoxia and amino acid neurotransmitter generation in the medulla. In: Frontiers in Arterial Chemoreception, edited by P. Zapata, C. Eyzaguirre, and R. W. Torrance. New York: Plenum, 1996, pp. 365–9.CrossRefGoogle Scholar
  6. 6.
    Lin, J, C. Suguihara, J. Huang, D. Hehre, C. Devia, and E. Bancalari. Effect of N-methyl-D-aspartate-re-ceptor blockade on hypoxic ventilatory response in unanesthetized piglets. J. Appl. Physiol. 80:1759–1763, 1996.PubMedGoogle Scholar
  7. 7.
    Mitra, J., N. R. Prabhakar, J. L. Overholt, and N. S. Cherniack. Respiratory effects of N-methyl-D-aspartate on the ventrolateral medullary surface. J. Appl. Physiol. 67:1814–1819, 1989.PubMedGoogle Scholar
  8. 8.
    Mtui, E. P., M. Anwar, R. Gomez, D. J. Reis, and D. A. Ruggiero. Projections from the nucleus tractus soli-tarii to the spinal cord. J Comp Neurol. 337:231–52, 1993.PubMedCrossRefGoogle Scholar
  9. 9.
    Mueller, R. A., D. B. A. Lundberg, G. R. Breese, J. Hedner, T. Hedner, and J Jonason. The neuropharmacology of respiratory control. Pharmacol. Rev. 34:255–85, 1982.PubMedGoogle Scholar
  10. 10.
    Paxinos, G., and C. Watson. The Rat Brain in Stereotaxic Coordinates. Sydney: Academic, 1982.Google Scholar
  11. 11.
    Soto-Arape, I., M. Burton, and H. Kazemi. Central amino acid neurotransmitters and the hypoxic ventilatory response. Am. J. Respir. Crit. Care Med. 151:1113–20, 1995.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • John L. Beagle
    • 1
  • Bernard Hoop
    • 1
  • Homayoun Kazemi
    • 1
  1. 1.Pulmonary and Critical Care Unit, Medical Services, Harvard Medical SchoolMassachusetts General HospitalBostonUSA

Personalised recommendations