Ventilatory and carotid body chemoreceptor responses to purinergic P2X receptor antagonists in newborn rats

Niane LM, Donnelly DF, Joseph V, Bairam A. Ventilatory and carotid body chemoreceptor responses to purinergic P2X receptor antagonists in newborn rats. J Appl Physiol 110: 83-94, 2011. First published November 4, 2010; doi:10.1152/japplphysiol.00871.2010.-Adenosine triphosphate, acting through purinergic P2X receptors, has been shown to stimulate ventilation and increase carotid body chemoreceptor activity in adult rats. However, its role during postnatal development of the ventilatory response to hypoxia is yet unknown. Using whole body plethysmography, we measured ventilation in normoxia and in moderate hypoxia (12% fraction of inspired O-2, 20 min) before and after intraperitoneal injection of suramin (P2X(2) and P2X(3) receptor antagonist, 40 mg/kg) in 4-, 7-, 12-, and 21-day-old rats. Suramin reduced baseline breathing (similar to 20%) and the response to hypoxia (similar to 30%) in all rats, with a relatively constant effect across ages. We then tested the effect of the specific P2X(3) antagonist, A-317491 (150 mg/kg), in rats aged 4, 7, and 21 days. As with suramin, A-317491 reduced baseline ventilation (similar to 55%) and the hypoxic response (similar to 40%) at all ages studied. Single-unit carotid body chemoreceptor activity was recorded in vitro in 4-, 7-, and 21-day-old rats. Suramin (100 mu M) and A-317491 (10 mu M) significantly depressed the sinus nerve chemosensory discharge rate (similar to 80%) in normoxia (PO2 similar to 150 Torr) and hypoxia (PO2 similar to 60 Torr), and this decrease was constant across ages. We conclude that, in newborn rats, P2X purinergic receptors are involved in the regulation of breathing under basal and hypoxic condition, and P2X(3)-containing receptors play a major role in carotid body function. However, these effects are not age dependent within the age range studied.