ENDOGENOUS ADENOSINE INHIBITS EVOKED SUBSTANCE-P RELEASE FROM PERIFUSED NETWORKS OF MYENTERIC GANGLIA

Isolated myenteric ganglion networks were prepared from guinea pig ile um and were used in a perifusion protocol to examine the effects of in terstitial adenosine on evoked release of substance P-like immunoreact ivity (SPLI). The release of SPLI evolved by elevated extracellular K concentration was increased in the presence of tetrodotoxin (TTX), in dicating tonic inhibition of SPLI release and revealing net inhibitory interganglionic transmission. Perifusion in the presence of the adeno sine A(1) receptor-selective antagonist 1,3-dipropyl-8-cyclopentylxant hine enhanced evolved SPLI release, which was further enhanced in the additional presence of TTX, indicating that adenosine contributes some , but not all, of the overall inhibitory tone within the networks. In addition to neural release of adenosine per se, an additional source w as investigated. Perifusion in the presence of alpha,beta-methylene-AD P plus guanosine 5'-monophosphate, which inhibits ecto-adenosinetripho sphatase (ATPase) activity enhanced SPLI release, indicating that hydr olysis of released ATP contributes to the total interstitial nucleosid e concentration and thereby to the overall inhibitory tone. It is conc luded that endogenous adenosine, some of which arises from ATP metabol ism, is an important contributor to the overall inhibitory tone presen t In myenteric ganglion networks.