cAMP elevation modulates physiological activity of pyloric neurons in the lobster stomatogastric ganglion.

1. We analyzed the physiological effects of the adenylate cyclase activator forskolin, and other adenosine 3',5'-cyclic monophosphate (cAMP)-elevating agents, on neurons of the pyloric circuit from the stomatogastric ganglion of the lobster Panulirus interruptus. Agents were bath applied to pyloric neurons either in the synaptically intact pyloric circuit or following isolation from all known synaptic input. 2. Several cAMP-elevating agents, including forskolin, 3-isobutyl-1-methylxanthine, Ro20-1724, and 8-bromo-cAMP, generated similar motor patterns from the pyloric circuit. The motor patterns exhibited an increased cycle frequency and enhanced spike activity from all classes of pyloric neurons. Since these agents differ both in structure and site of action in the cAMP pathway, their physiological effects on the motor pattern probably result from increased cAMP levels in pyloric neurons. 3. When forskolin was applied to synaptically isolated neurons, it caused a strong activation or enhancement of activity of all pyloric cells. However, it induced different types of activity in different cells, including the induction of bursting pacemaker potentials in one cell type, activation of plateau potentials in another, and depolarization with activation or enhancement of tonic spike activity in the remaining cells. Thus there is no single physiological response to cAMP elevation in the pyloric circuit; its effects can be quite diverse, mediating several activity states, in different cells. 4. Radioimmunoassays were performed on whole stomatogastric ganglia to determine whether known neuromodulators can affect cAMP concentrations. Both forskolin and octopamine increased cAMP levels, whereas dopamine, serotonin, proctolin, and FMRFamide did not appreciably affect cAMP levels. The physiological effects of octopamine and forskolin are similar in most, but not all, pyloric cells. Octopamine is thus a candidate neuromodulator whose actions may be mediated, at least in part, by increased cAMP in some pyloric cells; however, forskolin does not completely mimic the physiological effects of octopamine on all pyloric neurons, suggesting that octopamine can also act by other biochemical mechanisms.