[3H]adenosine uptake and release from synaptosomes. Alterations by barbiturates.

The effects of barbiturates on adenosine movements across the synaptic plasma membrane have been investigated using rodent whole brain synaptosomes. The hypothesis tested was that some of the depressant actions of these drugs may be mediated through interference with an endogenous adenosine system. Adenosine uptake was studied using synaptosomes prepared from Swiss-Webster mice. After preincubation at 37 degrees, [3H]adenosine was added to the synaptosomes in the presence or absence of pentobarbital, methohexital, phenobarbital, or 5-(2-cyclohexylideneethyl)-5-ethyl barbituric acid (CHEB) at various concentrations and times. All four compounds significantly inhibited [3H]adenosine uptake at concentrations of 100-300 microM. Pentobarbital did not affect the distribution of synaptosomal adenosine metabolites. Release of [3H]adenosine was studied using the P2 pellet from male CD-1 mice. Addition of 50 mM KCl caused an enhancement of 3H-efflux mainly due to increased release of adenosine and inosine. This effect was abolished in the presence of 250 microM ethylene glycol bis(beta-aminoethyl-ether)-N,N2-tetraacetic acid (EGTA). Pentobarbital, 0.3 mM, caused a significant increase in the net potassium-induced release of [3H]adenosine. These results suggest that some of the depressant effects of barbiturates may be due to inhibition of adenosine reuptake and enhancement of release resulting in elevated synaptic adenosine levels.