Central CO2chemoreception: a mechanism involving P2 purinoceptors localized in the ventrolateral medulla of the anaesthetized rat

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Abstract
The involvement of P2 purinoceptors in chemosensory function in the ventrolateral regions of the medulla oblongata was investigated in the anaesthetized rat. We have investigated the effect of antagonizing, or desensitizing, P2 receptors in the retrofacial area of the ventrolateral medulla on factors modifying respiratory activity. Bilateral microinjection of suramin (50 nl, 0.02 M), a P2 purinoceptor antagonist, into the retrofacial area in the artificially ventilated rat reduced resting phrenic nerve discharge. It also markedly affected the response of the phrenic nerve to increases in arterial CO2. Under conditions of hyperoxic, hypocapnic apnoea, the mean threshold for inducing phrenic nerve activity was raised significantly (from an end-tidal CO2 of 2.5 % to 4.5 %, n = 9). In addition, the slope of the respiratory response curve to increases in CO2 was reduced after suramin. A similar effect was observed after desensitization of certain P2X receptors with αβ-methyleneATP. As arterial levels of O2 were greater than 100 mmHg, and an equivalent pattern of response was observed in sino-aortically denervated and vagotomized animals, we believe any contribution of the peripheral chemoreceptors to be minimal. Our data suggest that respiratory neurones within the retrofacial area (Bötzinger complex) represent part of the central site of action of CO2 on respiration. Moreover, our observations lead us to suggest that CO2-evoked changes in respiration are mediated at least in part by P2X purinoceptors.