E. Ekblad et al., DISTRIBUTION, ORIGIN AND PROJECTIONS OF NITRIC-OXIDE SYNTHASE-CONTAINING NEURONS IN GUT AND PANCREAS, Neuroscience, 63(1), 1994, pp. 233-248
Nitric oxide has been put forward as an important inhibitory neurotran
smitter in the gut. Nitric oxide synthase-containing neurons were visu
alized by immunocytochemistry using antibodies against neuronal nitric
oxide synthase or by beta-nicotinamide adenine dinucleotide phosphate
diaphorase staining in whole mounts and cryostat sections from the ga
strointestinal tract and pancreas of several mammals (mouse, rat, hams
ter, guinea-pig, cat and man). Nitric oxide synthase-containing neuron
al cell bodies were numerous in the myenteric but fewer in the submuco
us ganglia all along the gut of all species. Varicose nerve terminals
formed extensive networks in the circular smooth muscle and the myente
ric ganglia. Nitric oxide synthase-containing nerve terminals were fre
quently found around the Brunner glands in the duodenum; scattered ner
ve terminals were also found in the gastric and colonic mucosa and aro
und blood vessels in the submucosa all along the gut. In the rat small
and large intestine nitric oxide synthase-containing submucous neuron
s terminated within the mucosa/submucosa and nitric oxide synthase-con
taining myenteric neurons issued short descending projections, approxi
mately 3 mm, to the smooth muscle and other myenteric ganglia. In the
pancreas of all species nitric oxide synthase-containing nerve cell bo
dies were regularly seen in intrapancreatic ganglia. Positive nerve fi
bers were mainly found within nerve trunks in interlobular spaces and
as delicate fibers within the islets. Double staining for nitric oxide
synthase and neuropeptides in intestine and pancreas of rat, guinea-p
ig and man revealed that only occasionally the nitric oxide synthase-c
ontaining nerve cell bodies stored in addition vasoactive intestinal p
eptide and neuropeptide Y, or enkephalin. However, nitric oxide syntha
se-containing nerve terminals, particularly those in the circular musc
le of the gut, frequently contained vasoactive intestinal peptide/neur
opeptide Y (rat and man) or vasoactive intestinal peptide/enkephalin (
guinea-pig). In intrapancreatic ganglia few nitric oxide synthase cont
aining nerve cell bodies were also vasoactive intestinal peptide-immun
oreactive. Coexistence of nitric oxide synthase and vasoactive intesti
nal peptide in nerve terminals could here be detected around blood ves
sels and interlobular ducts. The distribution of nitric oxide synthase
indicates a major role of nitric oxide in the regulation of gut motil
ity; a role in the regulation of blood flow and secretion in both gut
and pancreas is also likely.