Abstract
Acetylcholine (ACh) mediates neurotransmission at the neuromuscular junction and is involved in respiratory control1, notably chemosensitivity2 of central and peripheral origin. The level of ACh at the synaptic cleft and neuromuscular junction is regulated by the enzyme acetylcholinesterase (AChE). Blockade of AChE by organophosphorus compounds produces death by respiratory failure3, but despite the absence of AChE activity in all tissues, AChE (-/-) mice knockout for the gene coding for AChE develop to term4 and survive to adulthood if provided special care5. However, they show many aspects of a cholinergic syndrome, such as pinpoint pupils and muscle tremors5.
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References
A. Haji, R. Takeda, and M. Okazaki, Neuropharmacology of control of respiratory rhythm and pattern in mature mammals, Pharmacol. Ther. 86, 277–304 (2000).
M. D. Burton, and H. Kazemi, Neurotransmitters in central respiratory control, Respir. Physiol. 122, 111–121 (2000).
R. W. Brimblecombe, Drugs acting on cholinergic mechanisms and affecting respiration, in: Respiratory Pharmacology, edited by J. Widdicombe (Pergamon Press, Oxford, 1981), pp. 175–184.
W. Xie, J. A. Stribley, A. Chatonnet, P. J. Wilder, A. Rizzino, R. D. McComb, P. Taylor, S. H. Hinrichs, and O. Lockridge, Postnatal developmental delay and supersensitivity to organophosphate in gene-targeted mice lacking acetylcholinesterase, J. Pharmacol. Exp. Ther. 293, 896–902 (2000).
E. G. Duysen, J. A. Stribley, D. L. Fry, S. H. Hinrichs and O. Lockridge, Rescue of the acetylcholinesterase knockout mouse by feeding a liquid diet; phenotype of the adult acetylcholinesterase deficient mouse, Dev. Brain Res. 137, 43–54 (2002).
F. Chatonnet, E. Boudinot, A. Chatonnet, L. Taysse, S. Daulon, J. Champagnat, and A. S. Foutz, respiratory survival mechanisms in acetylcholinesterase knockout mouse, Eur. J. Neurosci. 18, 1419–1427 (2003).
A. S. Foutz, E. Boudinot, and M. Denavit-Saubié, Central respiratory depression induced by acetylcholinesterase inhibition: involvement of anaesthesia, Eur. J. Pharmacol. 142, 207–213 (1987).
A. S. Foutz, I.S. Delamanche, and M. Denavit-Saubié, Persistence of central respiratory rhythmogenesis after maximal acetylcholinesterase inhibition in unanaesthetized cats, Can. J. Physiol. Pharmacol. 67, 162–166 (1989).
M. D. Burton, D. C. Johnson, and H. Kazemi. The central respiratory effects of acetylcholine vary with CSF pH, J. Auton. Nerv. Syst. 62, 27–32. (1997).
X. M. Shao, and J. L. Feldman, Acetylcholine modulates respiratory pattern: effects mediated by M3-like receptors in pre-Bötzinger complex inspiratory neurons, J. Neurophysiol. 83, 1243–1252 (2000).
X. M. Shao, and J. L. Feldman, Mechanisms underlying regulation of respiratory pattern by nicotine in preBötzinger complex, J. Neurophysiol. 85, 2461–2467 (2001).
J. Minic, A. Chatonnet, E. Krejci, and J. Molgó, Butyrylcholinesterase and acetylcholinesterase activity and quantal transmitter release at normal and acetylcholinesterase knockout mouse neuromuscular junctions, Br. J. Pharmacol. 138, 177–187 (2003).
E. E. Nattie, and A. Li, Ventral medulla sites of muscarinic receptor subtypes involved in cardiorespiratory contro, J. Appl. Physiol. 69, 33–41 (1990).
A. Haji, S. Furuichi, and R. Takeda, Effects of iontophoretically applied acetylcholine on membrane potential and synaptic activity of bulbar respiratory neurones in decerebrate cats, Neuropharmacology 35, 195–203 (1996).
V. Bernard, C. Brana, I. Liste, O. Lockridge, and B. Bloch, Dramatic depletion of cell surface m2 muscarinic receptor due to limited delivery from intracytoplasmic stores in neurons of acetylcholinesterase-deficient mice, Mol. Cell. Neurosci. 23, 121–133 (2003).
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© 2004 Kluwer Academic/Plenum Publishers, New York
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Chatonnet, F., Boudinot, E., Chatonnet, A., Champagnat, J., Foutz, A.S. (2004). Breathing Without Acetylcholinesterase. In: Champagnat, J., Denavit-Saubié, M., Fortin, G., Foutz, A.S., Thoby-Brisson, M. (eds) Post-Genomic Perspectives in Modeling and Control of Breathing. Advances in Experimental Medicine and Biology, vol 551. Springer, Boston, MA. https://doi.org/10.1007/0-387-27023-X_25
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DOI: https://doi.org/10.1007/0-387-27023-X_25
Publisher Name: Springer, Boston, MA
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