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The effects of capsaicin (0.5‐100 microM) on neurones of the isolated inferior mesenteric ganglia (i.m.g.) of the guinea‐pig were investigated by means of intracellular recording techniques. When applied to neurones of the i.m.g. that exhibited a slow non‐cholinergic excitatory potential (Dun & Jiang, 1982), capsaicin caused in the large majority of these cells a long lasting depolarization accompanied by intense neuronal discharges. During and immediately following the depolarization, repetitive presynaptic stimulation consistently failed to elicit the non‐cholinergic depolarization; a partial recovery was observed in relatively few neurones. The fast (nicotinic) excitatory post‐synaptic potentials (e.p.s.p.s) were not suppressed by capsaicin in any of these cells. The membrane potential, input resistance and the amplitude of fast e.p.s.p.s in neurones of the i.m.g. that generated no detectable non‐cholinergic depolarizations were not affected by capsaicin. Post‐synaptic membrane sensitivity to exogenous application of substance P was not altered following capsaicin superfusion even though the latter effectively abolished the non‐cholinergic depolarization in the same neurones. Superfusing the i.m.g. with a Ca‐free Krebs solution markedly attenuated or abolished the depolarizing effect of capsaicin whereas tetrodotoxin (1 microM) was without effect. Capsaicin was without effect in a few neurones that generated a non‐cholinergic depolarization; the latter was not desensitized by bath application of substance P. Capsaicin caused no appreciable effects in neurones of the bullfrog sympathetic ganglia; thus, the fast and slow post‐synaptic potentials including the late slow e.p.s.p. the transmitter of which is the peptide luteinizing hormone‐releasing hormone (Jan & Jan, 1982) were not affected. The results suggest that the depolarizing effect of capsaicin in neurones of the guinea‐pig i.m.g. is due to a selective release of ganglionic substance P or a substance P‐like peptide in a Ca‐dependent manner, and that the non‐cholinergic potentials elicited in capsaicin‐insensitive neurones may be generated by a transmitter(s) other than substance P.

The nature of the putative transmitter(s) mediating the non‐cholinergic excitatory post‐synaptic potential (e.p.s.p.) described in the preceding paper was investigated by means of electrophysiological, pharmacological and immunohistochemical methods. Serotonin (1‐10 microM) when applied by superfusion caused a slow depolarization that closely mimicked the synaptic response in about 60% of the coeliac neurones 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 neurones 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 microM), a serotonin antagonist, and enhanced by fluoxetine (30‐50 microM), a serotonin reuptake inhibitor. On the other hand, pre‐treating the ganglia with L‐tryptophan (50 microM), a precursor of serotonin, preferentially augmented the synaptically induced response. A portion of the neurones (15%) were depolarized by substance P (1 microM) which also reversibly desensitized the non‐cholinergic e.p.s.p. elicited in these neurones. The remaining neurones (25%) were insensitive to either serotonin or substance P, and the non‐cholinergic e.p.s.p.s elicited in these cells were likewise not appreciably affected by these two agents. Furthermore, cyproheptadine, fluoxetine and L‐tryptophan had no significant effect on the non‐cholinergic e.p.s.p.s elicited in serotonin‐insensitive neurones. Using the immunohistofluorescent techniques, dense but unevenly distributed serotonin immunoreactive nerve fibres could be observed surrounding many coeliac neurones. Immunoreactivity was not observed in the ganglia incubated with antisera pre‐absorbed with excess serotonin. Collectively our results suggest that serotonin is the mediator of non‐cholinergic e.p.s.p.s. elicited in about 60% of coeliac neurones sampled in this study, and that in the remaining neurones the slow depolarization may be generated by substance P and/or some unknown transmitter(s).

Binding of radioactive vasopressin--but not of oxytocin--was detected by autoradiography and by labeling of membranes obtained from the rat superior cervical ganglion. In both instances binding could be displaced by V1 (smooth muscle-type) but not by V2 (kidney-type) agonists, indicating that the ganglionic vasopressin receptors are similar to those present on hepatocytes and vascular smooth muscle. In accordance with the V1 character of the receptors, vasopressin activated the turnover of membrane inositol lipids, and this effect was abolished by a structural analogue known to act as a vasopressor antagonist. A possible physiological role of vasopressin was suggested by intracellular recordings obtained from ganglion cells in vitro. Vasopressin induced a reduction in the amplitude of the fast excitatory postsynaptic potential evoked by electrical stimulation of the preganglionic nerve. This reduction in ganglionic transmission was antagonized by the same synthetic structural analogue that blocked the effect of vasopressin on inositol lipids. This study provides evidence for the presence of functional vasopressin receptors in a rat sympathetic ganglion and thus suggests that vasopressin may play a role in peripheral autonomic function.