Purinergic receptor blockade in the retrotrapezoid nucleus attenuates the respiratory chemoreflexes in awake rats

Acta Physiol (Oxf). 2016 May;217(1):80-93. doi: 10.1111/apha.12637. Epub 2015 Dec 29.


Aim: 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.

Conclusion: 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.

Keywords: adenosine triphosfate; breathing; central autonomic pathways; medulla oblongata; retrotrapezoid nucleus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology
  • Animals
  • Chemoreceptor Cells / metabolism*
  • Male
  • Medulla Oblongata / drug effects
  • Medulla Oblongata / metabolism*
  • Purinergic P2Y Receptor Antagonists / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Purinergic P2Y1 / metabolism*
  • Respiratory Physiological Phenomena*
  • Wakefulness


  • Purinergic P2Y Receptor Antagonists
  • Receptors, Purinergic P2Y1
  • Adenosine Triphosphate