title: Purinergic receptor blockade in the retrotrapezoid nucleus attenuates the respiratory chemoreflexes in awake rats.
abstract: OBJECTIVE
  Recent evidence suggests that adenosine triphosfate (ATP)-mediated purinergic signalling at the level of the rostral ventrolateral medulla contributes to both central and peripheral chemoreceptor control of breathing and blood pressure: neurones in the retrotrapezoid nucleus (RTN) function as central chemoreceptors in part by responding to CO2 -evoked ATP release by activation of yet unknown P2 receptors, and nearby catecholaminergic C1 neurones regulate blood pressure responses to peripheral chemoreceptor activation by a P2Y1 receptor-dependent mechanism. However, potential contributions of purinergic signalling in the RTN to cardiorespiratory function in conscious animals have not been tested.
  
  
  METHODS
  Cardiorespiratory activity of unrestrained awake rats was measured in response to RTN injections of ATP, and during exposure to hypercapnia (7% CO2 ) or hypoxia (8% O2 ) under control conditions and after bilateral RTN injections of P2 receptor blockers (PPADS or MRS2179).
  
  
  RESULTS
  Unilateral injection of ATP into the RTN increased cardiorespiratory output by a P2-receptor-dependent mechanism. We also show that bilateral RTN injections of a non-specific P2 receptor blocker (pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate (PPADS) reduced the ventilatory response to hypercapnia (7% CO2 ) and hypoxia (8% O2 ) in unanesthetized rats. Conversely, bilateral injections of a specific P2Y1 receptor blocker (MRS2179) into the RTN had no measurable effect on ventilatory responses elicited by hypercapnia or hypoxia.
  
  
  CONCLUSIONS
  These data exclude P2Y1 receptor involvement in the chemosensory control of breathing at the level of the RTN and show that ATP-mediated purinergic signalling contributes to central and peripheral chemoreflex control of breathing and blood pressure in awake rats.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Science, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: B F
authors.initials: BF
authors.lastname: Barna
authors.affiliation: Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: A C
authors.initials: AC
authors.lastname: Takakura
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, USA.
authors.forename: D K
authors.initials: DK
authors.lastname: Mulkey
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Science, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: T S
authors.initials: TS
authors.lastname: Moreira
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002628:Chemoreceptor Cells / Q000378:metabolism*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism*; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D058472:Receptors, Purinergic P2Y1 / Q000378:metabolism*; D012143:Respiratory Physiological Phenomena; D014851:Wakefulness
chemical_list: D058921:Purinergic P2Y Receptor Antagonists; D058472:Receptors, Purinergic P2Y1; D000255:Adenosine Triphosphate
keywords: adenosine triphosfate; breathing; central autonomic pathways; medulla oblongata; retrotrapezoid nucleus