Cyclic 3',5'-adenosine monophosphate mimics slow synaptic excitation in myenteric plexus neurons

Iontophoretic injection of cyclic adenosine monophosphate (cAMP) into the somas of ganglion cells in the myenteric plexus of guinea pig small intestine mimicked the slow excitatory postsynaptic potentials that occur in these neurons. These effects were: (1) membrane depolarization. (2) decreased membrane conductance, (3) augmented excitability with increased probability of spontaneous spike discharge and increased spike discharge during depolarizing current pulses, (4) anodal break excitation, (5) suppression of hyperpolarizing afterpotentials. The same effects were produced by application of membrane-permeable analogs of cAMP in the bathing medium. The phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, potentiated the effects of the analogs. The results suggest that the biochemical basis for long-lasting excitatory neuromodulation in myenteric neurons is activation of adenylate cyclase and elevation of intraneuronal cAMP.