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

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 O₂, 20 min) before and after intraperitoneal injection of suramin (P2X₂ and P2X₃ receptor antagonist, 40 mg/kg) in 4-, 7-, 12-, and 21-day-old rats. Suramin reduced baseline breathing (∼20%) and the response to hypoxia (∼30%) in all rats, with a relatively constant effect across ages. We then tested the effect of the specific P2X₃ antagonist, A-317491 (150 mg/kg), in rats aged 4, 7, and 21 days. As with suramin, A-317491 reduced baseline ventilation (∼55%) and the hypoxic response (∼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 μM) and A-317491 (10 μM) significantly depressed the sinus nerve chemosensory discharge rate (∼80%) in normoxia (Po₂ ∼150 Torr) and hypoxia (Po₂ ∼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 P2X₃-containing receptors play a major role in carotid body function. However, these effects are not age dependent within the age range studied.