Nitric oxide has been proposed as an inhibitory transmitter molecule that plays a role in muscle relaxation and vasodilation in the gastrointestinal tract. The present study analyzes the distribution of nitric‐oxide‐producing neurons in the monkey and human digestive system by means of nicotinamide‐adenine‐dinucleotide‐phosphate‐diaphorase histochemistry. This histochemical method is reliable and convenient for the visualization of neuronal nitric‐oxide synthase, the enzyme responsible for nitric‐oxide generation. In the gastrointestinal tract, nitric‐oxide‐synthase‐related diaphorase activity was present in nerve fibers running through‐out the muscle layer (circular > longitudinal) and in numerous ganglion cells and processes in the myenteric plexus of monkeys and humans. Labelled ganglion cells and fibers also were observed in the submucous plexus, although they were much less numerous than those seen in the myenteric plexus. In the submucosa, a few positive fibers were seen around blood vessels. In the mucosa, stained fibers were sparse at the base of the villi and crypts, whereas they were quite abundant in the muscularis mucosae, especially in the small intestine and colon. In the gallbladder (human), labelling was found in ganglion cells and processes of the innermost and outermost ganglionated plexuses. Stained fibers also were distributed to the muscular layer and, less abundantly, to the mucosa and vasculature. Labelled fibers were more abundant in the sphincter of Oddi (human) than in the gallbladder. In the monkey and human pancreas, nicotinamide‐adenine‐dinucleotide‐diaphorase staining was seen mainly in ganglion cells and fibers of intrapancereatic ganglia, and in processes running among acini, around ducts and in the stroma. A moderate density of stained fibers also was distributed to the vasculature, whereas the islets showed few positive processes. Finally, double label experiments performed in the pancreas showed that the vast majority of neurons producing intric oxide are immunoreactive for vasoactive intestinal peptide. The present results demonstrate that in the digestive tract of primates nitric‐oxide neurons and processes are widespread. This supports the hypothesis that neural nitric oxide plays a broader role than smooth‐muscle relaxation and vasodilation in the periphery. It may be involved in neuronal communication within the enteric plexuses and may influence different digestive functions including endocrine and exocrine secretions.
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