Background: To provide a morphological basis for understanding the role of nitric oxide in the pancreas, the present study was designed to clarify the localization and distribution of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) activity, a marker of NO synthase, in the pancreas of several mammalian species, including humans. Methods: NADPH-d activity was examined in the rat, guinea pig, dog, and human pancreas by histochemistry. In addition, the possibility of coproduction of NO and vasoactive intestinal polypeptide (VIP) was investigated by a combined use of histochemistry and immunohistochemistry. Results: In the pancreas, NADPH-d activity was localized in nerve fibers, nerve cell bodies, and the vascular endothelium. Nerve fibers with the enzyme activity were chiefly distributed in the exocrine pancreas and showed species differences in the distribution. Nerve fibers stained for NADPH-d were also observed in the endocrine pancreas, but the enzyme activity was not detected in the islet cells. Part of the nerve fibers and nerve cell bodies coexpressed NADPH-d activity and VIP-immunoreactivity. Conclusions: These results suggest that NO may act as a neuronal mediator and an endothelium-derived relaxing factor and may physiologically interact with VIP in the mammalian pancreas.
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