Effects of phenytoin on the release of 14C-adenine derivatives.

The release of 14C-containing compounds from rat cortical slices prelabeled with 14C-adenine consisted largely of adenosine (6-7%), inosine (13-18%), and hypoxanthine (70-74%), with small amounts of nucleotides including cyclic AMP and adenine. This efflux was increased by both ouabain (0.1 mM) and veratridine (0.05 mM), the increment in released radioactivity consisting almost entirely of these three compounds. However, relatively more inosine than adenosine output was evoked by ouabain while the reverse was true with veratridine. Phenytoin partially reversed the effect of both depolarizing agents. After prelabeling, the efflux from astrocytoma cell cultures contained predominantly inosine (74%) and hypoxanthine (23%) with little adenosine. Ouabain increased the release of 14C-adenine derivatives, and this increase was diminished by phenytoin. Preliminary studies with neuroblastoma cell cultures have shown considerable variability in the composition of the effluent, with hypoxanthine the prevalent compound and almost no adenosine. Ouabain enhanced the efflux from these cells, and this effect was apparently reversed by phenytoin.