Endogenous interstitial adenosine in isolated myenteric neural networks varies inversely with prevailing Po-2

Isolated myenteric ganglion networks were used in a perifusion protocol to characterize the response of interstitial adenosine levels to changes in pr evailing Po-2. The biological activity of such adenosine was assessed using inhibition of release of substance P (SP) as a functional measure of adeno sine activity, and the effect of altered O-2 tension on both spontaneous an d elevated extracellular K+ concentration-evoked SP release from networks w as determined over a range of Po, values from hypoxic (Po-2 = 54 mmHg) to h yperoxic (Po-2 = 566 mmHg). Release of SP was found to be sensitive to Po-2 , and a linear graded relationship was obtained. Perifusion in the addition al presence of the adenosine A1-receptor-selective antagonist 1,3-dipropyl- 8-cyclopentyl-xanthine (DPCPX) revealed considerable adenosinergic inhibiti on with an inverse exponential relationship and hyperoxic threshold Pot. Di sinhibition 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 a denosine released during hypoxia. A postulated neuroprotective role for ade nosine is consistent with the demonstrated relationship between interstitia l adenosine and prevailing O-2 tension.