The time course of
adenosine release in the nucleus tractus solitarii (NTS) and ventrolateral medulla (VLM) during acute systemic
hypoxia was investigated in the anaesthetised rat by means of amperometric enzymatic sensors. It was found that acute
hypoxia induced a significant delayed increase in
adenosine level (reaching levels as high as 5 microM) in the NTS and that
hypoxia-induced release of
adenosine was similar at various regions of the NTS along its rostro-caudal axis. Significantly smaller or no increases in
adenosine levels at all in response to
hypoxia were observed in the VLM. The increase in
adenosine level in the NTS occurred during reoxygenation after the termination of the hypoxic challenge and was accompanied by a smaller increase in
inosine concentration. At the dorsal surface of the brainstem, only release of
inosine was detected following acute
hypoxia. Addition of the
ecto-5'-nucleotidase inhibitor
alpha,beta-methylene ADP (200 microM) to the dorsal surface of the brainstem completely abolished the signal evoked by
hypoxia, suggesting that the
inosine arose from
adenosine that was produced in the extracellular space by the prior release of
ATP. This study indicates that following systemic
hypoxia,
adenosine levels in the NTS increase to a significantly greater extent than in the VLM. However, the increase in
adenosine concentration in the NTS occurs too late to be responsible for the
hypoxia-induced depression of the respiratory activity.