Xanthine derivatives IBMX and S-9977-2 potentiate transmission at an Aplysia central cholinergic synapse

In an attempt to investigate the role of cAMP-dependent phosphorylations on synaptic transmission at an Aplysia cholinergic buccal ganglion synapse, the effects of xanthine derivatives such as 3-isobutyl-1-methylxanthine (IBMX), which is well known to inhibit phosphodiesterase activity thereby promoting cAMP accumulation, and a novel xanthine derivative, S-9977-2 were evaluated. They were found to potentiate cholinergic transmission by significantly increasing the time constant of decay (Tc) of inhibitory postsynaptic currents (IPSCs). The postsynaptic origin of the phenomenon was supported by the observation that responses to the ionophoretic application of acetylcholine (ACh) were also potentiated in duration as well as in amplitude. No effects of S-9977-2 on the ACh-gated Cl- channel conductance or mean open time were observed. The finding that responses to the hydrolysis-resistant cholinergic analogue carbachol were unaffected by the two xanthines suggested that the observed effects were at least partly caused by an inhibition of acetylcholinesterase (AChE) activity. That these substances inhibit AChE activity was confirmed in vitro. Phosphorylation processes nonetheless appear to be partly involved in the synaptic effect of the xanthines as the kinase blocker H-8 blocked part of the IPSC Tc lengthening. Possible mechanisms are discussed.