ATP as a mediator of mammalian central CO2 chemoreception.
1. A role for P2 purinoceptors in the chemosensory response of respiratory neurones localised in the ventrolateral medulla to changes in arterial CO2 levels was investigated in the anaesthetised rat. Extracellular recordings were made from different classes of respiratory neurone and the effects of P2 receptor blockade on CO2-evoked changes in activity investigated. 2. Increasing inspired CO2 excited 85 % of inspiratory neurones in the pre-Botzinger complex. In all cases, CO2-evoked excitation was blocked by ionophoretic application of the P2 receptor antagonists suramin (0.02 M) and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 100 microM), but not the adenosine receptor antagonist 8-phenyltheophylline (8-PT; 100 microM). Suramin and PPADS often reduced ongoing activity, and blocked the excitatory effects of ATP. Inspiratory neurones were also excited by the P2X receptor agonist alphabeta-methyleneATP, suggesting a specific role for P2X receptors. 3. Sixty-six per cent of pre-inspiratory neurones were also excited by CO2. This effect was reduced or abolished by prior application of P2 receptor antagonists. Although post-inspiratory and expiratory neurones were excited by increasing levels of CO2, and also by ionophoretically applied ATP, the CO2-evoked effects were unaffected by P2 receptor blockade. 4. We suggest that ATP, possibly acting via P2X purinoceptors localised within the ventral respiratory group, is involved in central chemoreception. Specifically, these distinctive CO2-P2X-mediated actions were observed only in inspiratory neurones (incrementing inspiratory neurones and pre-inspiratory neurones), which appear to have purinoceptors with pH sensitivity that can account for the actions of CO2 in modifying ventilatory activity.
Thomas
T
T
Autonomic Neuroscience Institute, Department of Physiology, Royal Free and University College Medical School, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK.
Spyer
K M
KM
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002245:Carbon Dioxide / Q000097:blood* / Q000494:pharmacology; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007478:Iontophoresis; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism*; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D058915:Purinergic P1 Receptor Antagonists; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013498:Suramin / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D058915:Purinergic P1 Receptor Antagonists; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D002245:Carbon Dioxide; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D013498:Suramin; D000255:Adenosine Triphosphate; D013806:Theophylline; C028322:8-phenyltheophylline; C002630:alpha,beta-methyleneadenosine 5'-triphosphate