Noradrenergic innervation of serotoninergic neurons in the myenteric plexus.

The monoaminergic innervation of the guinea pig small intestine was investigated to determine if there is an anatomical basis for the hypothesis that serotoninergic and noradrenergic neurons physiologically interact in the enteric nervous system. Initial rates of uptake of tritiated 5-hydroxytryptamine (3H-5-HT) or norepinephrine (3H-NE) by segments of guinea pig small intestine were measured in order to estimate the regional density of the serotoninergic and noradrenergic innervation. No change was found in the uptake of 3H-5-HT as a function of distance between duodenum and ileum, whereas the relative uptake of 3H-NE declined. The pattern of serotoninergic elements demonstrated radioautographically was compared with that obtained by visualizing 5-HT immunoreactivity. Both methods revealed that a small number of serotoninergic neurons, located in 35.3% +/- 1.5% of myenteric ganglia, give rise to many fibers that form thick bundles in interganglionic connectives. Moreover, there was a pronounced heterogeneity in the serotoninergic innervation of individual myenteric neurons and ganglia. In material fixed with aldehydes and postfixed with NaMnO4, noradrenergic axon terminals were identified by their characteristic small dense-cored vesicles. Following incubation with 3H-NE only terminals with small dense-cored vesicles were radioautographically labeled, confirming that these terminals are noradrenergic. When 3H-5-HT was substituted for 3H-NE, noradrenergic terminals were not labeled, showing that nonspecific uptake of 3H-5-HT into noradrenergic axons did not occur in the presence of 5-hydroxydopamine. The combination of aldehyde-NaMnO4 fixation with the radioautographic localization of 3H-5-HT thus permitted the simultaneous identification of serotoninergic and noradrenergic neural elements. Serotoninergic varicosities were found to differ from noradrenergic varicosities in the size, appearance, and packing density of their synaptic vesicles. In addition, recognizable but rudimentary pre- and postsynaptic membrane specializations were associated with serotoninergic but not noradrenergic varicosities. Most serotoninergic neuronal cell bodies were contacted both by serotoninergic synapses and noradrenergic varicosities. Similar appositions of noradrenergic varicosities with nonserotoninergic neurons appeared to be rare. In view of earlier observations that sympathetic nerves affect the release of 5-HT from stimulated enteric serotoninergic neurons, it seems likely that the noradrenergic appositions with serotoninergic neurons are the anatomical substrate for this effect.(ABSTRACT TRUNCATED AT 400 WORDS)