Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The number of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d)-positive cells in the myenteric plexus increased 1 week after surgical extrinsic denervation of a loop of guinea pig ileum. NADPH-d staining in submucosal ganglia and vasoactive intestinal polypeptide immunoreactivity in submucosal and myenteric ganglia were not affected by denervation. Similar data were obtained after systemic capsaicin, but not 6-hydroxy-dopamine treatment, suggesting that loss of primary afferents increases NADPH-d staining. Increases in NADPH-d may be part of an adaptive process allowing normal gut function after loss of extrinsic nerves.
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PMID:Extrinsic denervation increases NADPH diaphorase staining in myenteric nerves of guinea pig ileum. 751 42

The origin and distribution of cerebral perivascular nerves containing nitric oxide, a short-acting messenger or neurotransmitter, have been studied in the rat by histochemistry for reduced nicotinamide adenine dinucleotide phosphate-diaphorase activity, a specific marker for neuronal nitric oxide synthase. Positively stained nerve fibers were distributed throughout the major vessels of the cerebral arteries, though the fiber density was higher in the anterior circulation, including the circle of Willis, than in the posterior arteries. Examination using axonal transport methods indicated that nitric oxide-containing neurons in the sphenopalatine ganglion innervate the cerebral arteries bilaterally. Nitric oxide synthase in these ganglionic cells often co-existed with vasoactive intestinal polypeptide. The anatomical information obtained is discussed in terms of non-adrenergic, non-cholinergic neuronal transmission in the cerebral arteries.
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PMID:Projections of nitric oxide synthase-containing fibers from the sphenopalatine ganglion to cerebral arteries in the rat. 752 85

The distribution of neurons that are capable of synthesizing nitric oxide (NO) has been demonstrated in the porcine large intestine by means of NO synthase (NOS) immunocytochemistry and nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochemistry. An overall colocalization of NOS immunoreactivity and NADPHd staining was observed. Nitrergic neurons were abundant in the myenteric and outer submucous plexus of the caecum, colon, and rectum. Only a few nitrergic perikarya were seen in the inner submucous plexus of the colon and caecum, whereas a substantially larger number was observed in the rectum. Nitrergic nerve fibers were present in the three ganglionic nerve plexuses. Contrary to the outer longitudinal muscle layer and the mucosal region, the circular muscle layer received a dense nitrergic innervation. The nitrergic nerve cells were variable in size and shape, and several displayed vasoactive intestinal polypeptide (VIP) immunoreactivity (IR). Retrograde tracing studies revealed the existence of nitrergic neurons that project to the caudal (inferior) mesenteric ganglion. They were observed in the myenteric and outer submucous plexus of the transverse and descending colon and the rectum. These observations strongly suggest that several subpopulations of NO-synthesizing neurons, namely, motor neurons and interneurons, should be distinguished in the porcine large intestine, thereby emphasizing the importance of NO as a biologically active mediator.
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PMID:Nitric oxide synthase-containing neurons in the pig large intestine: topography, morphology, and viscerofugal projections. 752 72

The distribution, colocalisation, and interconnections of nitrinergic and peptidergic neurons and nerves in the human oesophagus were examined. Cryosections of surgically resected tissues from eight subjects were studied with indirect immunofluorescence for the presence of 11 neuropeptides and neuron specific enolase. After immunohistochemistry, nitric oxide synthase was shown on the same sections with the beta nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemical reaction. The histochemical findings were verified immunohistochemically on other sections with an antiserum against nitric oxide synthase. Most myenteric neurons (55%) were nitrinergic. Most (96%) received terminations positive for vasoactive intestinal polypeptide (VIP), calcitonin gene related peptide (CGRP) (80%), and galanin (59%). The neuronal somata of 14% also contained VIP, while 10% had galanin. Of the NADPH-diaphorase containing fibers seen in the muscle layers, many had closely associated VIP and galanin, but only rarely CGRP and substance P. Thus, despite abundant representation of both peptidergic and nitrinergic systems in oesophageal smooth muscle, only VIP and galanin colocalised to any significant extent with the nitrinergic elements. These findings provide morphological support for the role of nitric oxide as the non-adrenergic non-cholinergic inhibitory mediator in the human oesophagus and for its possible interactive role with the peptidergic system.
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PMID:Nitrinergic and peptidergic innervation of the human oesophagus. 753 Feb 28

Nitric oxide (NO) is synthesized in neurons and is a potent relaxor of vascular and nonvascular smooth muscle. The uterus contains abundant NO-synthesizing nerves which could be autonomic and/or sensory. This study was undertaken to determine: 1) the source(s) of NO-synthesizing nerves in the rat uterus and 2) what other neuropeptides or transmitter markers might coexist with NO in these nerves. Retrograde axonal tracing, utilizing Fluorogold injected into the uterine cervix, was employed for identifying sources of uterine-projecting neurons. NO-synthesizing nerves were visualized by staining for nicotinamide adenine dinucleotide phosphate (reduced)-diaphorase (NADPH-d) and immunostaining with an antibody against neuronal/type I NO synthase (NOS). NADPH-d-positive perikarya and terminal fibers were NOS-immunoreactive (-I). Some NOS-I/NADPH-d-positive nerves in the uterus are parasympathetic and originate from neurons in the pelvic paracervical ganglia (PG) and some are sensory and originate from neurons in thoracic, lumbar, and sacral dorsal root ganglia. No evidence for NOS-I/NADPH-d-positive sympathetic nerves in the uterus was obtained. Furthermore, double immunostaining revealed that in parasympathetic neurons, NOS-I/NADPH-d-reactivity coexists with vasoactive intestinal polypeptide, neuropeptide Y, and acetylcholinesterase and in sensory nerves, NOS-I/NADPH-d-reactivity coexists with calcitonin gene-related peptide and substance P. In addition, tyrosine hydroxylase(TH)-I neurons of the PG do not contain NOS-I/NADPH-d-reactivity, but some TH-I neurons are apposed by NOS-I varicosities. These results suggest NO-synthesizing nerves in the uterus are autonomic and sensory, and could play significant roles, possibly in conjunction with other putative transmitter agents, in the control of uterine myometrium and vasculature.
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PMID:Nitric oxide nerves in the uterus are parasympathetic, sensory, and contain neuropeptides. 753 54

Congenital esophageal stenosis (CES) is a rare disorder with narrowed esophageal lumen that presents as dysphagia from childhood and that is often associated with tracheobronchial remnants or webs. The pathogenesis of CES is unknown. The aim of this study was to examine the histological and immunohistochemical features of CES. Esophagi from 2 young adults with CES and 3 controls with no motility disorders underwent routine H&E staining, trichrome staining for collagen, and detailed immunocytochemical studies for general neuronal markers (protein gene product 9.5, neuron-specific enolase, and S-100) and neurotransmitters (vasoactive intestinal polypeptide, substance P, and galanin) and nitric oxide synthase by beta-nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase and a specific NO synthase antibody. Quantitative experiments compared the numbers of myenteric neurons and amounts of fibers at the circular muscle. CES esophagi showed infiltration of neutrophils in the myenteric plane, without any increase in collagen. NADPH-diaphorase histochemistry showed a significant reduction of myenteric nitrinergic neurons (7 +/- 3.4 vs. 2.7 +/- 1.8 neurons per high-power field) and fibers at the circular muscle. Other peptidergic neurons studied were not significantly reduced in CES. The specific total lack of NO inhibitory innervation may be an important mechanism in the pathogenesis of stenosis and aperistalsis of the esophagus in this disorder.
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PMID:Peptidergic and nitrinergic denervation in congenital esophageal stenosis. 754 Oct

Nitric-oxide-releasing nerves regulate esophageal smooth muscle function. The density of such nerve fibers may differ in the different functional parts of the esophagus. We used both inspection and gray-scale analysis of digitized images to seek differences in density of such nerve fibers, stained for reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-diaphorase), between esophageal body and esophago-gastric sphincter and between smooth muscle layers in the opossum esophagus. Sections of Swiss roll preparations of the entire organ were stained for NADPH-diaphorase and for immunoreactivity to vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), galanin (GAL), substance P (SP) and constitutive nitric oxide synthase (cNOS). In the circular muscle layer, NADPH-diaphorase-positive fibers were most abundant at the cephalic end of the esophageal body with a significant decline toward and through the esophago-gastric sphincter. In the longitudinal muscle layer and the longitudinally-oriented muscularis mucosae, NADPH-diaphorase-positive nerve fibers were most abundant at the esophago-gastric sphincter with a significant decline toward and through the striated-smooth muscle junction. cNOS immunoreactivity co-localized with NADPH-diaphorase activity. Fibers stained for CGRP immunoreactivity were distributed like the NADPH-diaphorase-positive fibers. Fibers stained for immunoreactivity to the other peptides (VIP, GAL, SP) showed no clear differences in distribution along the esophagus in any of the muscle layers.
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PMID:NADPH-diaphorase-positive nerve fibers in smooth muscle layers of opossum esophagus: gradients in density. 754 93

The distribution of nitric oxide synthase-immunoreactive (NOS-IR) axons and their relationship to structures immunoreactive to vasoactive intestinal polypeptide (VIP), substance P (SP) and tyrosine hydroxylase (TH) were studied by means of the nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) technique or double-labelling immunofluorescence in the genital organs of cow and pig. Relevant neurons were also investigated in the pig. NOS-containing neural structures were TH-immunonegative in bovine or porcine genital organs, or in the studied ganglia. In the bovine ovary, NOS-IR nerves were neither VIP-IR nor SP-IR, whereas in the pig, most NOS-containing axons were also VIP-IR. The oviduct was supplied by single NOS/VIP- or NOS/SP-containing nerves, whereas in the uterus, NOS-IR axons were moderate in number, often being immunoreactive for VIP or SP. Numerous NOS/VIP-IR and NOS/SP-IR nerves were found in the vagina of both species. In all tissues studied, NOS-IR axons were mainly related to vascular smooth muscle. Most of the neurons of the paracervical ganglia and some neurons in dorsal root ganglia exhibited strong NOS activity. Only single neurons in sympathetic ganglia were NADPH-d-positive. Most nitrergic neurons in the autonomic ganglia were VIP-IR but SP-immunonegative. The sensory neurons were mostly NOS/SP-IR, whereas only single neurons co-expressed NOS and VIP immunoreactivity.
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PMID:The distribution and co-localization of immunoreactivity to nitric oxide synthase, vasoactive intestinal polypeptide and substance P within nerve fibres supplying bovine and porcine female genital organs. 755 66

Quinone reductase [NAD(P)H:(quinone acceptor) oxidoreductase, EC 1.6.99.2], also called DT diaphorase, is a homodimeric FAD-containing enzyme that catalyzes obligatory NAD(P)H-dependent two-electron reductions of quinones and protects cells against the toxic and neoplastic effects of free radicals and reactive oxygen species arising from one-electron reductions. These two-electron reductions participate in the reductive bioactivation of cancer chemotherapeutic agents such as mitomycin C in tumor cells. Thus, surprisingly, the same enzymatic reaction that protects normal cells activates cytotoxic drugs used in cancer chemotherapy. The 2.1-A crystal structure of rat liver quinone reductase reveals that the folding of a portion of each monomer is similar to that of flavodoxin, a bacterial FMN-containing protein. Two additional portions of the polypeptide chains are involved in dimerization and in formation of the two identical catalytic sites to which both monomers contribute. The crystallographic structures of two FAD-containing enzyme complexes (one containing NADP+, the other containing duroquinone) suggest that direct hydride transfers from NAD(P)H to FAD and from FADH2 to the quinone [which occupies the site vacated by NAD(P)H] provide a simple rationale for the obligatory two-electron reductions involving a ping-pong mechanism.
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PMID:The three-dimensional structure of NAD(P)H:quinone reductase, a flavoprotein involved in cancer chemoprotection and chemotherapy: mechanism of the two-electron reduction. 756 29

The localization of nitric oxide synthase, the enzyme responsible for producing the short-acting messenger nitric oxide, has been determined in the digestive tract of the rat using histochemistry for reduced nicotinamide adenine dinucleotide phosphate-diaphorase activity, a specific marker for neuronal nitric oxide synthase. Positively stained neurons were found throughout the entire digestive tract from the esophagus to the rectum. Positive neuronal somata were very common in the myenteric ganglia. Dense positive fibers were distributed in internodal strands, the secondary plexus, the tertiary plexus, and were particularly abundant in the deep muscular plexus, while very few were observed in the submucosal ganglia. The density of these positive structures was higher in the small and large intestine than in the esophagus and stomach. The pattern of distribution suggested that some of these positive cells innervate gut muscles. Double-staining revealed that in these enteric neurons, nitric oxide synthase does not co-localize with acetylcholinesterase. Instead, vasoactive intestinal polypeptide almost always coexists with nitric oxide synthase in the myenteric plexus. Thus, nitric oxide and vasoactive intestinal polypeptide may be co-transmitters in a population of non-adrenergic, non-cholinergic neurons in the enteric nervous system.
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PMID:Histochemical localization of nitric oxide synthase in rat enteric nervous system. 768 13


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