A selective adenosine antagonist (8-cyclopentyl-1,3-dipropylxanthine) eliminates both neuromuscular depression and the action of exogenous adenosine by an effect on A₁ receptors

The effect of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective A₁ adenosine receptor antagonist, was studied at frog motor nerve endings in the hope of determining whether the inhibitory effects of exogenous or endogenous adenosine on neurotransmitter release are mediated by an A₁ receptor or the postulated prejunctional "A₃ receptor." These putative A₃ receptors have been reported to have a lower affinity for DPCPX (≫1 nM) than A₁ receptors (50-190 pM) and have been linked to changes in Ca²⁺ translocation. The affinity of DPCPX as an antagonist of exogenous adenosine at frog motor nerve endings was calculated by using the Schild equation and found to range from 25 to 200 pM (n = 12). These values are consistent with the presence of A₁ receptors. The effect of endogenous adenosine as a mediator of prejunctional neuromuscular depression produced by repetitive nerve impulses was fully reversed by 100 pM DPCPX. Neither prejunctional neuromuscular depression produced by endogenous or exogenous adenosine nor the reversal of depression by DPCPX was associated with changes in nerve terminal Ca²⁺ currents. The results demonstrate that endogenous or exogenous adenosine mediates neuromuscular depression in the frog, via an A₁ receptor.