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This Article Free via Open Access: OA OA Full Text Full Text (PDF) OA All Versions of this Article: 585/1/305    most recent jphysiol.2007.143933v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gourine, A. V. Articles by Gourine, V. N. Search for Related Content PubMed PubMed Citation Articles by Gourine, A. V. Articles by Gourine, V. N. Related Collections Integrative

¹ Department of Physiology, University College London, Gower Street, London WC1E 6BT, UK
² Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK
³ Institute of Physiology, National Academy of Sciences of Belarus, Minsk 220725, Belarus

Receptors for extracellular ATP (both ionotropic and metabotropic) are widely expressed in the CNS both in neurones and glia. ATP can modulate neuronal activity in many parts of the brain and contributes to the central nervous control of several physiological functions. Here we show that during the systemic inflammatory response the extracellular concentrations of ATP increase in the anterior hypothalamus and this has a profound effect on the development of the thermoregulatory febrile response. In conscious rabbits we measured ATP release in real time with novel amperometric biosensors and monitored a marked increase in the concentration of ATP (4.0 ± 0.7 µM) in the anterior hypothalamus in response to intravenous injection of bacterial endotoxin – lipopolysaccharide (LPS). No ATP release was observed in the posterior hypothalamus. The release of ATP coincided with the development of the initial phase of the febrile response, starting 18 ± 2 min and reaching its peak 45 ± 2 min after LPS injection. Application of the ATP receptor antagonists pyridoxal-5'-phosphate-6-azophenyl-2',4'-disulphonic acid, Brilliant Blue G or periodate oxidized ATP dialdehyde to the site of ATP release in the anterior hypothalamus markedly augmented and prolonged the febrile response. These data indicate that during the development of the systemic inflammation, ATP is released in the anterior hypothalamus to limit the magnitude and duration of fever. This release may also have a profound effect on the hypothalamic control of other physiological functions in which ATP and related purines have been implicated to play modulatory roles, such as food intake, hormone secretion, cardiovascular activity and sleep.

(Received 27 August 2007; accepted after revision 26 September 2007; first published online 27 September 2007)
Corresponding author A. V. Gourine: Department of Physiology, University College London, Gower Street, London WC1E 6BT, UK. Email: a.gourine{at}ucl.ac.uk

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