Evidence for a serotonin-mediated slow excitatory potential in the guinea-pig coeliac ganglia.

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Abstract
The nature of the putative transmitter(s) mediating the non-cholinergic excitatory post-synaptic potential (e.p.s.p.) described in a preceding paper was investigated by means of electrophysiological, pharmacological and immunohistochemical methods. Serotonin (1-10 .mu.M) when applied by superfusion caused a slow depolarization that closely mimicked the synaptic response in about 60% of the celiac neurons that exhibited a non-cholinergic e.p.s.p. The serotonin depolarization evoked in low-Ca2+, high-Mg2+ solution or in a Krebs solution containing cholinergic antagonists was quantitatively similar to that elicited in normal Krebs solution. When compared in the same neurons the membrane resistance change during the course of the serotonin depolarization and of the non-cholinergic e.p.s.p., as well as their respective responses to conditioning polarization, were similar. The non-cholinergic e.p.s.p. was reversibly abolished during serotonin-induced depolarization; the blockade persisted when the membrane potential was restored to the resting level by hyperpolarizing current. The serotonin depolarization as well as the non-cholinergic e.p.s.p. were reversibly suppressed by cyproheptadine (20-50 .mu.M), a serotonin antagonist and enhanced by fluoxetine (30-50 .mu.M), a serotonin reuptake inhibitor. On the other hand, pre-treating the ganglia with L-tryptophan (50 .mu.M), a precursor of serotonin, preferentially augmented the synaptically induced response. A portion of the neurons (15%) were depolarized by substance P (1 .mu.M) which also reversibly desensitized the non-cholinergic e.p.s.p. elicited in these neurons. The remaining neurons (25%) were insensitive to either serotonin or substance P and the non-cholinergic e.p.s.p. elicited in these cells were likewise not appreciably affected by these 2 agents. Furthermore, cyproheptadine, fluoxetine and L-tryptophan had no significant effect on the non-cholinergic e.p.s.p. elicited in serotonin-insensitive neurons. Using immunohistofluorescent techniques, dense but unevenly distributed serotonin immunoreactive nerve fibers could be observed surrounding many celiac neurons. Immunoreactivity was not observed in the ganglia incubated with antisera pre-absorbed with excess serotonin. Serotonin evidently is the mediator of non-cholinergic e.p.s.p. elicited in about 60% of celiac neurons sampled in this study. In the remaining neurons, the slow depolarization may be generated by substance P and/or some unknown transmitter(s).