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¹ Department of Physiology, Royal Free and University College London Medical School, London NW3 2PF, UK

Abstract

Peripheral and central respiratory chemoreceptors are ultimately responsible for maintenance of constant levels of arterial P_O2, P_CO2 and [H⁺], protecting the brain from hypoxia and ensuring that the breathing is always appropriate for metabolism. The aim of this discussion is to shed some light on the potential mechanisms of chemosensory transduction – the process which links chemosensory mechanisms to the central nervous mechanisms controlling breathing. Recent experimental data suggest that the purine nucleotide ATP acts as a common mediator of peripheral and central chemosensory transduction (within the carotid body and the medulla oblongata, respectively). In response to a decrease in P_O2 (hypoxia) oxygen-sensitive glomus cells of the carotid body release ATP to activate chemoafferent fibres of the carotid sinus nerve which transmit this information to the brainstem respiratory centres. In response to an increase in P_CO2/[H⁺] (hypercapnia) chemosensitive structures located on the ventral surface of the medulla oblongata rapidly release ATP, which acts locally within the medullary respiratory network. The functional role of ATP released at both sites is similar – to evoke adaptive enhancement in breathing. Understanding the mechanisms of ATP release in response to chemosensory stimulation may prove to be essential for further detailed analysis of cellular and molecular mechanisms underlying respiratory chemosensitivity.

(Received 4 August 2005; accepted after revision 30 August 2005; first published online 1 September 2005)
Corresponding author A. V. Gourine: Department of Physiology, Royal Free and University College Medical School, University College London, Hampstead Campus, Rowland Hill Street, London NW3 2PF UK. Email: a.gourine{at}medsch.ucl.ac.uk

This Wellcome Prize Lecture was given on 20 December 2004 at King's College London.

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