Effects of bivalent cations on adenosine sensitivity in the rat hippocampal slice

Ligand binding studies have demonstrated that bivalent cations can alter interactions between purinergic agonists and adenosine receptors in brain membranes. In the present study, we have investigated whether a similar interaction can be demonstrated in terms of a functional response to adenosine, which is the inhibition of synaptic transmission in the CA1 region of the rat hippocampus mediated via presynaptic A1 receptors. Our data suggest that alterations in cation concentrations do not significantly affect the sensitivity of these adenosine receptors, as long as changes are made in such a way as to leave presynaptic Ca2+ entry unaffected. The experimental results do not support the conclusion that there is a specific effect of either Ca2+ or Mg2+ on adenosine receptor sensitivity, such as has been described for agonist interactions with adenosine A1 receptors. We conclude that the effects of bivalent cations observed in ligand binding studies probably reflect an effect at an intracellular site, either on the receptor itself, or perhaps on associated GTP binding proteins.