Occlusive responses to adenosine A1 receptor and muscarinic M2 receptor activation on hippocampal presynaptic terminals

There is substantial evidence for an interaction between adenosine Al and muscarinic M1/M3 receptors in some tissues, either at the level of the receptors themselves or at the associated transduction system. We have now addressed the question of whether there is a similar interaction between Al and presynaptic M2 receptors in the hippocampus. The effects of cyclopentyladenosine (CPA) were studied alone or in combination with the M2 receptor agonist oxotremorine-M. The ability of both to depress synaptic transmission presynaptically at the concentrations used was confirmed using paired-pulse inhibition. When combined at a range of concentrations, the effects of the two agents were less than additive, suggesting that they are acting by a common transduction system. The results indicate that the modulatory, antagonistic effects of Al adenosine receptors are exerted not only on postjunctional M1/M3 receptors but also at M2 presynaptic receptors. (C) 1999 Elsevier Science B.V. All rights reserved.