IN APLYSIA SENSORY NEURONS, THE NEUROPEPTIDE SCP(B) AND SEROTONIN DIFFER IN EFFICACY BOTH IN MODULATING CELLULAR PROPERTIES AND IN ACTIVATING ADENYLYL-CYCLASE - IMPLICATIONS FOR MECHANISMS UNDERLYING PRESYNAPTIC FACILITATION

The facilitatory transmitters serotonin (5-HT) and the molluscan neuro peptides SCP(A) and SCP(B) both activate adenylyl cyclase in Aplysia m echanosensory neurons and produce multiple modulatory effects that con tribute to increasing transmitter release from these cells. This enhan cement of transmitter release from sensory neurons contributes to incr eased behavioral response during sensitization and classical condition ing in Aplysia. Recently, specific examples of modulation in these sen sory neurons have been described that are more effectively initiated b y 5-HT than by the SCPs. For example, in the present study, 5-HT produ ces 55% greater broadening of the normal sensory neuron action potenti al than did SCP(B). These differences in the modulatory actions of the facilitatory transmitters have been interpreted as suggesting that 5- HT produces its modulatory effects at least partly via a cAMP-independ ent mechanism. However, we have found that the two types of facilitato ry transmitters are not equally effective in activating adenylyl cycla se. In both whole CNS membranes and sensory neuron membranes. SCP(B) w as less effective than 5-HT in stimulating adenylyl cyclase activity m easured in steady state assays. Because electrophysiological experimen ts suggested that the response to the SCPs desensitizes rapidly, we fu rther compared cyclase stimulation in perfused membrane assays that en able continuous monitoring of cyclase activity; however we observed th at 5-HT was also more effective than SCP(B) in stimulating cyclase at the onset of transmitter exposure. We discuss the possibility that low er peak stimulation of cyclase by SCP(B) and a faster rate of desensit ization could account for some of the differences between the SCPs and 5-HT in modulating sensory neurons.