Endogenous interstitial adenosine in isolated myenteric neural networks varies inversely with prevailing P O 2

Isolated myenteric ganglion networks were used in a perifusion protocol to characterize the response of interstitial adenosine levels to changes in prevailing$P{O}_2$ . The biological activity of such adenosine was assessed using inhibition of release of substance P (SP) as a functional measure of adenosine activity, and the effect of altered O₂ tension on both spontaneous and elevated extracellular K⁺ concentration-evoked SP release from networks was determined over a range of$P{O}_2$ values from hypoxic ($P{O}_2$ = 54 mmHg) to hyperoxic ($P{O}_2$ = 566 mmHg). Release of SP was found to be sensitive to $P{O}_2$ , and a linear graded relationship was obtained. Perifusion in the additional presence of the adenosine A₁-receptor-selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) revealed considerable adenosinergic inhibition with an inverse exponential relationship and hyperoxic threshold $P{O}_2$ . Disinhibition of evoked SP release by DPCPX in the absence of TTX was double that observed in its presence, indicating a neural source for some of the adenosine released during hypoxia. A postulated neuroprotective role for adenosine is consistent with the demonstrated relationship between interstitial adenosine and prevailing O₂ tension.