Endogenous interstitial adenosine in isolated myenteric neural networks varies inversely with prevailing PO2.

Isolated myenteric ganglion networks were used in a perifusion protocol to characterize the response of interstitial adenosine levels to changes in prevailing![Formula][1] . 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![Formula][2] values from hypoxic (![Formula][3] = 54 mmHg) to hyperoxic (![Formula][4] = 566 mmHg). Release of SP was found to be sensitive to ![Formula][5] , 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 ![Formula][6] . 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. [1]: /embed/mml-math-2.gif [2]: /embed/mml-math-3.gif [3]: /embed/mml-math-4.gif [4]: /embed/mml-math-5.gif [5]: /embed/mml-math-6.gif [6]: /embed/mml-math-7.gif