MODULATION OF ADENOSINE RELEASE FROM RAT SPINAL-CORD BY ADENOSINE-DEAMINASE AND ADENOSINE KINASE INHIBITORS

Adenosine, a modulator of pain processing in the spinal cord, is metab olized by adenosine kinase and adenosine deaminase. In this study we d etermined which of these mechanisms is more important for the regulati on of endogenous adenosine levels in the rat spinal cord. The effects of the adenosine kinase inhibitors, 5'-amino-5'-deoxyadenosine (NH(2)d AD) and iodotubercidin (IOT), and the adenosine deaminase inhibitor, 2 '-deoxycoformycin (DCF), on adenosine release in a spinal cord superfu sion model were studied. DCF markedly increased basal adenosine levels detected in perfusates and was more potent than NH(2)dAD and IOT in t his regard. Coadministration of DCF with NH(2)dAD produced an enhanced effect compared to the inhibitors alone. NH(2)dAD, but not DCF, poten tiated morphine-evoked adenosine release. These results suggest that a denosine deaminase may be the predominant pathway for adenosine metabo lism in this experimental model.