Adenosine, Cyclic AMP and Nerve Conduction

Summary

The actions of adenosine, adenosine-stable analogues, adenine nucleotides, dibutyril cyclic AMP, methylxanthines, papaverine, and forskolin were studied on desheathed frog sciatic nerves partially inhibited with tetrodotoxin (TTX). All substances, but not the adenine nucleotides, which antagonized the inhibitory action of TTX on compound action potentials, decreased the amplitude of compound action potentials partially inhibited by TTX. The finding that substances which can increase cyclic AMP accumulation in nerve axons mimic the inhibitory action of adenosine on nerve conduction suggests that the effect of adenosine is positively coupled to the adenylate cyclase/cyclic AMP system. The interpretation that the inhibitory effect of adenosine on nerve conduction can result from a reduction in the sodium entry during the action potential is supported by the finding that the most potent adenosine analogue that enhances the TTX-induced axonal blockade, N⁶-cyclohexyladenosine (CHA), decreases the uptake of ²²Na by rat brain synaptosomes stimulated by veratridine. Whether the present results might help to explain the anticonvulsant properties of adenosine is discussed.