Purinergic modulation of respiration via medullary raphe nuclei in rats

The involvement of P2X receptors in raphe nuclei in respiratory control was investigated. Experiments were done on urethane anesthetized, spontaneously breathing or paralyzed and artificially ventilated adult rats. We found that microinjection of ATP (0.1–0.2 M, 10–70 nl) into raphe magnus (RM) caused dose-dependent decreases in integrated phrenic amplitude and respiratory frequency, whereas injection of ATP into raphe pallidus (RP) caused dose-dependent increases in phrenic amplitude and respiratory frequency. Microinjection of pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS) (0.02 M, 50 nl), a broad-spectrum P2X receptor antagonist, into the RM or RP did not cause any significant change in respiration, but partially blocked the respiratory effects of ATP that was subsequently injected into the same sites within the RM or RP. These findings indicate that the ATP–P2X mediated neurotransmission could contribute to the respiratory control by affecting the activities of raphe nuclei.