Gourine, Alexander V., Dale, Nicholas, Korsak, Alla, Llaudet, Enrique, Tian, Faming, Huckstepp, Robert T. R. and Spyer, K. Michael. (2008) Release of ATP and glutamate in the nucleus tractus solitarii mediate pulmonary stretch receptor (Breuer-Hering) reflex pathway. The Journal of Physiology, Vol.586 (No.16). pp. 3963-3978. ISSN 0022-3751

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Abstract

The Breuer-Hering inflation reflex is initiated by activation of the slowly adapting pulmonary stretch receptor afferents (SARs), which monosynaptically activate second-order relay neurones in the dorsal medullary nucleus of the solitary tract (NTS). Here we demonstrate that during lung inflation SARs release both ATP and glutamate from their central terminals to activate these NTS neurones. In anaesthetized and artificially ventilated rats, ATP- and glutamate-selective microelectrode biosensors placed in the NTS detected rhythmic release of both transmitters phase-locked to lung inflation. This release of ATP and glutamate was independent of the centrally generated respiratory rhythm and could be reversibly abolished during the blockade of the afferent transmission in the vagus nerve by topical application of local anaesthetic. Microionophoretic application of ATP increased the activity of all tested NTS second-order relay neurones which receive monosynaptic inputs from the SARs. Unilateral microinjection of ATP into the NTS site where pulmonary stretch receptor afferents terminate produced central apnoea, mimicking the effect of lung inflation. Application of P2 and glutamate receptor antagonists (pyridoxal-5'-phosphate-6-azophenyl-2',4'-disulphonic acid, suramin and kynurenic acid) significantly decreased baseline lung inflation-induced firing of the second-order relay neurones. These data demonstrate that ATP and glutamate are released in the NTS from the central terminals of the lung stretch receptor afferents, activate the second-order relay neurones and hence mediate the key respiratory reflex - the Breuer-Hering inflation reflex.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry Q Science > QP Physiology
Divisions:	Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010)
Library of Congress Subject Headings (LCSH):	Adenosine triphosphate, Glutamic acid, Reflexes, Neurons, Solitary nucleus
Journal or Publication Title:	The Journal of Physiology
Publisher:	Blackwell
ISSN:	0022-3751
Date:	15 August 2008
Volume:	Vol.586
Number:	No.16
Number of Pages:	16
Page Range:	pp. 3963-3978
Identification Number:	10.1113/jphysiol.2008.154567
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Wellcome Trust (London, England)
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URI:	http://wrap.warwick.ac.uk/id/eprint/29503

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