Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.5.2 (NQO1)
 6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serotoninergic and cholinergic neurons are known to appear earlier in the ontogeny (day E12) of the murine gut than those containing substance P or vasoactive intestinal peptide (day E14). It has also been demonstrated that proliferating neural precursors coexist with mature neurons in developing enteric ganglia. These observations have led to the hypotheses that peptidergic neurons develop later than those that utilize small molecule neurotransmitters and that the activity of early developing neurons may affect the phenotypic expression of coexisting neuroblasts. As a partial test of these hypotheses we studied the phenotypic expression of neurons recognized by antisera to neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP), and of those visualized by the histochemical demonstration of reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase activity. NADPH diaphorase activity, which is coexpressed with NPY immunoreactivity in all submucosal and many myenteric neurons, was first found on day E11 in clusters of cells in the dorsal mesogastrium. These cells also expressed neurofilament reactivity and thus were developing along a neuronal lineage. Enteric neurons that expressed NADPH diaphorase activity were visualized in the stomach one day later, on day E12. At this time, NADPH diaphorase-containing cells could no longer be demonstrated in the dorsal mesogastrium. NPY immunoreactivity first appeared in the wall of the bowel on day E12, when it was seen in cells in the presumptive stomach. By day E13, the entire length of the bowel contained NPY-immunoreactive neurons. Cells that displayed NADPH diaphorase activity were found at this time at both ends of the alimentary tract, but did not appear in the ileum until day E18. In contrast, CGRP immunoreactivity could not be detected anywhere in the gut until day E17, but by day E18 all regions of the bowel contained CGRP-immunoreactive neurons. Endogenous 5-HT was first detected at day E16 in mucosal epithelial cells in all segments of the gut except the stomach, where it appeared at day E18. The NPY/NADPH diaphorase set of neurons thus develop before the acquisition of a detectable level of endogenous 5-HT or enteric neural 5-HT receptors (which arise in the foregut at day E14). These observations demonstrate that enteric neurons that express small molecule neurotransmitters do not necessarily develop earlier than peptidergic neurons as a class; however, various types of enteric neurons do appear in a sequential order.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Time course of expression of neuropeptide Y, calcitonin gene-related peptide, and NADPH diaphorase activity in neurons of the developing murine bowel and the appearance of 5-hydroxytryptamine in mucosal enterochromaffin cells. 278 79

Nitric oxide synthase-like immunoreactivity was found in a subpopulation of sympathetic postganglionic neurons in the cat stellate and lower lumbar ganglia. In the ganglia of other segments such cells were rare. Double staining for tyrosine hydroxylase-like immunoreactivity and nitric oxide synthase-like immunoreactivity or the reduced nicotinamide adenine dinucleotide phosphate diaphorase reaction indicated that nitric oxide synthase-like immunoreactivity and reduced nicotinamide adenine dinucleotide phosphate diaphorase reactivity was always co-localized and was confined to tyrosine hydroxylase-negative (presumably cholinergic) ganglion cells, and was present in most of them. The occurrence of nitric oxide synthase in two subpopulations of cholinergic postganglionic neurons was investigated in triple staining experiments. Presumptive sudomotor neurons have been previously defined as scattered cells containing calcitonin gene-related peptide-like immunoreactivity, usually accompanied by vasoactive intestinal peptide-like immunoreactivity: 99% of these contained nitric oxide synthase. Presumptive muscle vasodilator neurons have been previously identified as clumped cells with strong vasoactive intestinal peptide-like immunoreactivity but no calcitonin gene-related peptide-like immunoreactivity: 70% of these contained nitric oxide synthase. Sweat glands were found in the paw pad skin surrounded by varicose fibres showing calcitonin gene-related peptide-like immunoreactivity and vasoactive intestinal peptide-like immunoreactivity, confirming previous work. Such fibres also stained for nitric oxide synthase-like immunoreactivity and reduced nicotinamide adenine dinucleotide phosphate diaphorase reactivity, although their staining was relatively weaker than in the corresponding cell bodies. Varicose fibres with the same chemical coding were also found around all large and most medium and small arteries in the paw skin as well as around arteriovenous anastomoses. Fibres with the muscle vasodilator coding (vasoactive intestinal peptide-like immunoreactivity without calcitonin gene-related peptide-like immunoreactivity) were not seen in paw skin. These results suggest that nitric oxide may act as a co-transmitter (with acetylcholine, substance P, vasoactive intestinal peptide and calcitonin gene-related peptide) in sudomotor neurons and (with acetylcholine and vasoactive intestinal peptide) in vasodilator neurons. Collateral branches of sudomotor neurons may innervate skin vessels, and release vasodilator transmitters including nitric oxide to cause the vasodilatation which provides the fluid supply for sweat formation. Alternatively, separate vasodilator neurons to skin may share the same chemical code as sudomotor neurons.
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PMID:Nitric oxide synthase and chemical coding in cat sympathetic postganglionic neurons. 747 30

The architecture and neurochemistry of the enteric nervous system was studied by use of whole-mount preparations obtained by microdissection of the horse jejunum. A myenteric plexus and two plexuses within the submucosa were identified. The external submucosal plexus lying in the outermost region of the submucosa had both neural and vascular connections with the inner submucosal plexus situated closer to the mucosa. Counts of neurones stained for NADH-diaphorase demonstrated the wide variation in size, shape and neurone content of individual ganglia in both the external and internal submucosal plexuses. The average number of cells/ganglion was similar in each plexus (about 25 cells). Immunoreactivities for galanin, vasoactive intestinal peptide and neuropeptide Y were observed in nerve cell bodies and fibres of each of the plexuses. Immunoreactivity for substance P was extensive and strong in nerve fibres of all plexuses but was weaker in cell bodies of the submucosal neurones and absent in the cell bodies of the myenteric plexus. Comparative quantitative analysis of immunoreactive cell populations with total cell numbers (enzyme staining) was indicative of neuropeptide colocalization in the external submucosal plexus.
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PMID:Structural organization and neuropeptide distributions in the equine enteric nervous system: an immunohistochemical study using whole-mount preparations from the small intestine. 752 Mar 62

Recent studies in physiology have suggested that part of the inhibitory nonadrenergic noncholinergic (iN-ANC) response of airway smooth muscle is mediated by nitric oxide (NO). To examine this point morphologically, the guinea pig respiratory tract was investigated histochemically for nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase (NADPH-d), a marker for NO synthase (NOS). In addition, coexpression of NOS and vasoactive intestinal peptide (VIP) or calcitonin gene-related peptide (CGRP) was studied using a combination of histochemistry for NADPH-d and immunohistochemistry for VIP or CGRP. Nerve fibers showing NADPH-d activity were abundantly observed in the respiratory tract. They were distributed throughout smooth-muscle bundles, lamina propria, submucosal glands, and around bronchial and pulmonary arteries. NADPH-d-containing nerve-cell bodies were occasionally found within airway ganglia. The colocalization study demonstrated that NADPH-d-containing nerve fibers frequently coincided with VIP-like immunoreactive nerve fibers but not with CGRP-like immunoreactive nerve fibers. Among nonneural tissues, NADPH-d activity was noticed in the endothelium of both bronchial and pulmonary vessels, and in the pleura. These observations indicated that NO may be produced by neurons and vascular endothelium of the guinea pig respiratory tract, and may function as a neuronal mediator as well as endothelium-derived relaxing factor (EDRF). Colocalization of NADPH-d and VIP-like immunoreactivity in nerve fibers suggested that NO and VIP may function as cotransmitters.
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PMID:NADPH-diaphorase activity as a marker for nitric oxide synthase in neurons of the guinea pig respiratory tract. 752 81

The lack of nonadrenergic, noncholinergic (NANC) inhibitory innervation in aganglionic intestine is typical of Hirschsprung's disease. Several neuropeptides participating in the intestinal NANC innervation are greatly reduced in aganglionic intestine. However, these findings do not fully explain the pathophysiology of the disease. Recently, nitric oxide (NO) has been presented as a potent smooth muscle relaxant, and the enzyme responsible for its formation, nitric oxide synthase (NOS) has been demonstrated in neuronal elements in both the central and peripheral nervous system. In our study, nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining, a marker for NOS, and NOS immunohistochemistry revealed a dense innervation of the smooth muscle layers and the myenteric ganglia in ganglionic non afflicted intestine from patients with Hirschsprung's disease. By contrast, there was an almost complete lack of NOS-immunoreactive and NADPH-diaphorase-positive nerve fibers in the afflicted aganglionic bowel. NOS and vasoactive intestinal peptide were found to be partially colocalized in nerve fibers and neuronal cell bodies in the ganglionic but not in the aganglionic intestine. The lack of NO-producing nerve fibers in the aganglionic intestine probably contributes to the inability of the smooth muscle to relax, thereby causing lack of peristalsis in Hirschsprung's disease.
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PMID:Lack of neuronal nitric oxide synthase in nerve fibers of aganglionic intestine: a clue to Hirschsprung's disease. 753 32

Nitric oxide has been put forward as an important inhibitory neurotransmitter in the gut. Nitric oxide synthase-containing neurons were visualized 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 gastrointestinal tract and pancreas of several mammals (mouse, rat, hamster, guinea-pig, cat and man). Nitric oxide synthase-containing neuronal cell bodies were numerous in the myenteric but fewer in the submucous ganglia all along the gut of all species. Varicose nerve terminals formed extensive networks in the circular smooth muscle and the myenteric ganglia. Nitric oxide synthase-containing nerve terminals were frequently found around the Brunner glands in the duodenum; scattered nerve terminals were also found in the gastric and colonic mucosa and around blood vessels in the submucosa all along the gut. In the rat small and large intestine nitric oxide synthase-containing submucous neurons terminated within the mucosa/submucosa and nitric oxide synthase-containing myenteric neurons issued short descending projections, approximately 3 mm, to the smooth muscle and other myenteric ganglia. In the pancreas of all species nitric oxide synthase-containing nerve cell bodies were regularly seen in intrapancreatic ganglia. Positive nerve fibers 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-pig and man revealed that only occasionally the nitric oxide synthase-containing nerve cell bodies stored in addition vasoactive intestinal peptide and neuropeptide Y, or enkephalin. However, nitric oxide synthase-containing nerve terminals, particularly those in the circular muscle of the gut, frequently contained vasoactive intestinal peptide/neuropeptide Y (rat and man) or vasoactive intestinal peptide/enkephalin (guinea-pig). In intrapancreatic ganglia few nitric oxide synthase-containing nerve cell bodies were also vasoactive intestinal peptide-immunoreactive. Coexistence of nitric oxide synthase and vasoactive intestinal peptide in nerve terminals could here be detected around blood vessels and interlobular ducts. The distribution of nitric oxide synthase indicates a major role of nitric oxide in the regulation of gut motility; a role in the regulation of blood flow and secretion in both gut and pancreas is also likely.
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PMID:Distribution, origin and projections of nitric oxide synthase-containing neurons in gut and pancreas. 753 82

The intramural projections of nerve cells containing serotonin (5-HT), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and nitric oxide synthase or reduced nicotinamide adenine dinucleotide phosphate diaphorase (NOS/NADPHd) were studied in the ascending colon of 5- to 6-week-old pigs by means of immunocytochemistry and histochemistry in combination with myectomy experiments. In control tissue of untreated animals, positive nerve cells and fibres were common in the myenteric and outer submucous plexus and, except for 5-HT-positive perikarya, immunoreactive cell bodies and fibres were also observed in the inner submucous plexus. VIP- and NOS/NADPHd-positive nerve fibres occurred in the ciruclar muscle layer while VIP was also abundant in nerve fibres of the mucosal layer. 5-HT- and CGRP-positive nerve fibres were virtually absent from the aganglionic nerve networks. In the submucosal layer, numerous paravascular CGRP-immunoreactive (IR) nerve fibres were encountered. Myectomy studies revealed that 5-HT-, CGRP-, VIP- and NOS/NADPHd-positive myenteric neurons all displayed anal projections within the myenteric plexus. In addition, some of the serotonergic myenteric neurons projected anally to the outer submucous plexus, whereas a great number of the VIP-ergic and nitrergic myenteric neurons send their axons towards the circular muscle layer. The possible function of these nerve cells in descending nerve pathways in the porcine colon is discussed in relation to the distribution pattern of their perikarya and processes and some of their morphological characteristics.
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PMID:Projections of neurochemically specified neurons in the porcine colon. 754 65

The distribution of neuronal nitric oxide synthase (NOS) immunoreactivity was examined in rat and rabbit retinas and was compared with the distribution of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase reactivity and vasoactive intestinal peptide (VIP) immunoreactivity. An antibody raised against a C-terminal fragment of a cloned rat cerebellar NOS was used to localise NOS immunoreactivity. NOS immunoreactive cells were not detected in rat retinas at postnatal day 1 or 4, but were seen from postnatal day 7 onwards. NOS immunolabelling was seen in a small population of cells in the proximal inner nuclear layer. Most of the labelled cells had the position of amacrine cells and were seen to send processes into the inner plexiform layer. A few labelled cells were at times also seen in the ganglion cell layer, which are likely to correspond to displaced amacrine cells. The same NOS-labelling pattern was seen in rat and rabbit retinas. NADPH-diaphorase staining was observed in both species, in photoreceptor inner segments, in cells with the position of horizontal cells, in a subset of amacrine and displaced amacrine cells, in large cell bodies in the ganglion cell layer, in both plexiform layers, and in endothelium. Colocalisation of NOS immunoreactivity and NADPH-diaphorase staining was only observed among amacrine cells. However, not all NADPH-diaphorase-reactive amacrine cells were found to be NOS immunoreactive. VIP immunoreactivity was also localised in rat retinas in a subpopulation of amacrine cells, but no colocalisation of NOS and VIP immunoreactivity was observed. Our observations indicate that only amacrine cells contain the NOS form recognisable by the antibody used, and suggest that different isoforms of neuronal NOS may be present in retinal cells. Further, the onset of NOS expression in rat amacrine cells appears to occur independently of neuronal activity.
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PMID:Localisation of neuronal nitric oxide synthase-immunoreactivity in rat and rabbit retinas. 754 85

In the cat carotid body, nitric oxide synthase (NOS) immunoreactivity and NADPH diaphorase activity localize in nerve fibers mainly associated with blood vessels and occasionally lying close to glomus cells. The NOS-positive innervation originates in part from multipolar ganglion cells scattered in and around the carotid body and in the glossopharyngeal nerve. In the superior cervical ganglion, NOS and diaphorase staining localizes to many preganglionic axons and also to a small population of vasoactive intestinal peptide-positive, presumably cholinergic, ganglion cells. Positively stained ganglion cells are absent in the petrosal ganglion and very rare in the nodose ganglion, although both sensory ganglia display characteristic distributions of cells immunoreactive for calcitonin gene-related peptide, substance P and tyrosine hydroxylase. The NOS-positive innervation of the carotid body thus appears to be autonomic, originating mainly from a population of dispersed ganglion cells, and probably parasympathetic in nature. The superior cervical ganglion also may supply some pre- or postganglionic NOS-positive axons. Nitric oxide released from these nerves could affect glomus cell activity directly or indirectly by vasoregulation.
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PMID:Nitric oxide synthase in autonomic innervation of the cat carotid body. 759 14

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 throughout the muscular 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 intrapancreatic 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 nitric oxide are immunoreactive for vasoactive intestinal peptide.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nitric oxide producing neurons in the monkey and human digestive system. 804 Mar 67


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