ADENOSINE KINASE INHIBITORS AUGMENT RELEASE OF ADENOSINE FROM SPINAL-CORD SLICES

Inhibitors of adenosine kinase, but not adenosine deaminase, produce a ntinociception when administered spinally. In this study, we evaluated the relative contribution of adenosine kinase and adenosine deaminase to the regulation of adenosine release into the extracellular space w ithin the spinal cord by determining the effects of the adenosine kina se inhibitors 5'-amino-5'-deoxyadenosine and 5-iodotubercidin, and the adenosine deaminase inhibitor 2'-deoxycoformycin on adenosine release from spinal cord slices in an in vitro perfusion system. Both 5'-amin o-5'-deoxyadenosine (5-50 mu M) and 5-iodotubercidin (5-50 mu M), but not 2'-deoxycoformycin (50 mu M), augmented adenosine release. 5-Iodot ubercidin was slightly more potent and effective than 5'-amino-5'-deox yadenosine in augmenting release except at the highest concentration, where it was considerably more effective. Combinations of 2'-deoxycofo rmycin (50 mu M) and minimally active concentrations of 5'-amino-5'-de oxyadenosine and 5-iodotubercidin (5 mu M each) produced a synergistic enhancement of release. These results support a predominant involveme nt of adenosine kinase in regulating extracellular adenosine levels in the spinal cord, but adenosine deaminase also can play a significant role.