The role of serotonin in non-cholinergic excitatory transmission in the guinea pig inferior mesenteric ganglion.

The non-cholinergic late slow excitatory postsynaptic potential (ls-EPSP) of the guinea pig inferior mesenteric ganglion (IMG) was previously believed to be mediated by substance P (SP) or several other neuropeptides. Yet, the pharmacological evidence presented here indicates that serotonin (5-HT) may be another transmitter for the ls-EPSP in the guinea pig IMG. Repetitive stimulation of the presynaptic nerves elicited ls-EPSP in about half of the IMG neurons. Application of 5-HT or SP caused, in a portion of the IMG neurons, a slow depolarization similar to ls-EPSP. Fifty-six out of 88 (63.6%) neurons with ls-EPSP and 13 out of 35 (37.1%) neurons with ls-EPSP were sensitive to 5-HT and SP, respectively. Superfusion of the ganglia with 5-HT markedly suppressed the ls-EPSP evoked in 5-HT sensitive neurons. Similarly, exogenously applied SP attenuated the ls-EPSP of SP-sensitive neurons. However, prolonged superfusion of 5-HT or SP had no effect on the ls-EPSP elicited in 5-HT or SP-insensitive neurons, respectively. Furthermore, the ls-EPSPs elicited in 5-HT-sensitive neurons as well as the 5-HT-induced depolarization were reversibly suppressed by cyproheptadine, a 5-HT antagonist, and enhanced by fluoxetine, a 5-HT reuptake inhibitor. In contrast, the ls-EPSP of 5-HT insensitive neurons and SP-induced depolarization were not appreciably changed by those two drugs. Pretreatment with p-chlorophenylalanine, a 5-HT biosynthesis inhibitor, did not change the general electrophysiological characteristics of the neurons and did not suppress nicotinic neurotransmission, but markedly reduced the occurrence rate of ls-EPSP from 53.8% to 15.1% (P less than 0.005). Collectively, our results indicate that, besides SP, 5-HT may be involved in mediating the ls-EPSP in a subpopulation of neurons in the guinea pig IMG. The type of transmitter mediating ls-EPSP is apparently not limited to 5-HT and SP, as about 30% of the neurons with ls-EPSP were found to be insensitive to both 5-HT and SP and prolonged superfusion with both did not affect appreciably the ls-EPSP elicited in these neurons.