Pulsatile application of serotonin (5-HT) leads to facilitation of excitatory postsynaptic potentials (EPSPs) in crayfish "opener" neuromuscular preparations. The facilitation resulting from a single application of serotonin shows two phases: an early, rapidly decaying phase, and a less intense, long-lasting phase of 1- to 2-h duration. A previous study implicated the phosphatidylinositol system as an essential component in serotonin-induced facilitation, especially the early phase. The present study was conducted to determine the roles of the adenylate cyclase and phosphatidylinositol systems in both phases of serotonin-induced facilitation. 2. Relatively brief applications of agents known to affect the intracellular concentration of cAMP (forskolin, 1 microM; and IBMX, 100 microM) cause an increase in EPSP amplitude, which persists for 1-2 h. 3. The duration of the less intense, long-lasting phase of serotonin-induced facilitation is prolonged in the presence of 1 microM IBMX. This concentration of IBMX does not affect EPSP amplitude by itself. A membrane-permeant analog of cAMP (applied in concentrations less than or equal to 1 mM) is also not effective in altering EPSP amplitude. However, when dibutyryl cAMP is applied in the presence of 1 microM IBMX, EPSP amplitude is increased (60-80%). 4. Localized presynaptic injection of the "Walsh Inhibitor" (PKI), which inhibits cAMP-activated protein kinase, blocks the less intense, long-lasting phase of serotonin-induced facilitation at synapses near the site of injection. Normal facilitation develops at synapses within the same preparation remote from the site of injection. Distribution of the injected inhibitor within the axon can be visualized by tagging PKI with a fluorescent marker.(ABSTRACT TRUNCATED AT 250 WORDS)
