Neurotransmitter modulation, phosphodiesterase inhibitor effects, and cyclic AMP correlates of afterdischarge in peptidergic neurites

Abstract
The neuroendocrine bag cells in the abdominal ganglion of Aplysia californica generate a long-lasting synchronous afterdischarge upon brief stimulation of an afferent pathway. After this afterdischarge the cells become refractory to further synaptic stimulation. Synchrony, afterdischarge and prolonged refractoriness are properties that can be expressed in the isolated asomatic neurites of the bag cells. Two independent types of refractoriness were detected. The 1st (type I) is seen as a failure of action potentials generated in the tips of bag cell neurites to invade cell somata. The 2nd form of refractoriness (type II) controls the duration of afterdischarge such that stimuli after the 1st afterdischarge produce only very short afterdischarges or fail to elicit an afterdischarge. Type II refractoriness is sensitive to serotonin [5-hydroxytryptamine] and certain of its analogues, and to dopamine and the methylxanthine phosphodiesterase inhibitors. Extracellularly applied serotonin suppresses an ongoing afterdischarge while dopamine and the phosphodiesterase inhibitors, when applied at the end of the 1st afterdischarge, generate a subsequent afterdischarge of long duration without further electrical stimulation. None of these compounds influenced the degree of type I refractoriness. Serotonin and dopamine stimulated the formation of cyclic [c] AMP in the bag cell clusters and in the pleurovisceral connectives, and the occurrence of an afterdischarge was associated with a specific increase in total cAMP in bag cell bodies. Afterdischarges could be generated in unstimulated preparations by extracellular application of the cAMP analogues, 8-benzylthio-cAMP or 8-methylthio-cAMP. Serotonin and/or dopamine may control bag cell activity and activation of adenylate cyclase may be linked to bag cell afterdischarge.