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:1.6.99.3 (diaphorase)
5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We had previously shown NADPH diaphorase activity in fixed tissue slices of the insular cortex of the Syrian golden hamster (Mesocricetus auratus). The objective of this work was to determine the chemical identity of agents responsible for the observed NADPH diaphorase activities. Three different enzymatic NADPH diaphorase activities were distinguished in the insular cortex. (a) The activity seen in endothelial cells was not characterized histochemically, but it co-localized with eNOS-like immunoreactivity. (b) The neuronal Type I activity showed little sensitivity to 10(-5) M dicoumarol, could use either alpha- or beta-NADPH with almost equal facility, and co-localized with nNOS-like immunoreactivity. This activity was primarily attributable to nNOS. (c) The neuronal Type II activity was greatly attenuated by 10(-5) M dicoumarol, had a strong preference for beta-NADPH (rather than alpha-NADPH), and did not co-localize with any NOS-like immunoreactivity. These characteristics also apply to the NADPH diaphorase activity observed in the diffuse blue band in Layers II and III of agranular and dysgranular insular cortex and in the meshwork of cortical fibers. This staining was due primarily to a dicoumarol-sensitive dehydrogenase(s), either an isozyme of DT diaphorase (EC 1.6.99.2), or NADPH dehydrogenase (quinone) (EC 1.6. 99.6), or to a novel dicoumarol-sensitive NADPH dehydrogenase.
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PMID:NOS- and non-NOS NADPH diaphorases in the insular cortex of the Syrian golden hamster. 988 55

Several studies, including histochemical ones, have indicated that nitric oxide (NO) of endothelial origin may be related to the pulmonary vasodilation that occurs at birth. Since no histologic studies have been done of the possible parallel perinatal increase in production of neuronal NO synthase (nNOS) by pulmonary nerve plexuses, we investigated the distribution of nNOS in fetal, neonatal, and adult mouse lung. Lungs from mice aged 13 d gestation to 6 d after birth and lungs of adults were studied through histochemistry for nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) activity and immunocytochemistry. Both techniques gave almost similar results in relation to time of appearance, distribution, and frequency of neural structures positive for NADPH-d and NOS. NADPH-d staining was also applied to whole mounts of developing and adult tracheae. Staining was found from gestational days 13 to 15 onward in a small portion of the neuronal population. In all stages studied, NADPH-d/NOS staining was found in neuron cell bodies in the hilar region and bronchiolar wall, as well as in neuronal processes. Labeled terminal nerve fibers with varicosities were more frequent in pulmonary blood vessels than in airways. In tracheae, similar NADPH-d/NOS-positive nerve plexuses were found. The presence of nNOS in fetal and neonatal mouse respiratory tract suggests that neurally derived NO must play a role in developing lung physiology. However, because no perinatal increase in the number or intensity of staining of nNOS-positive nerve structures was seen, no apparent relation between neural NO and vasodilation can be established at birth.
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PMID:Histochemical demonstration of neuronal nitric oxide synthase during development of mouse respiratory tract. 992 27

Nitric oxide (NO) has been implicated as a retrograde signal in the process of refining axonal pathways during brain development. To determine some of the factors involved in this process, we have used two model pathway systems in the rat and mouse superior colliculus (SC). The first, the patch-cluster system, consists of clusters of neurons in the intermediate gray layer (igl) which transiently express NO during development and which receive input from a cholinergic pathway from the parabrachial brainstem as well as from other pathways containing different transmitters. The second system, the retinocollicular pathway, consists of glutamatergic fibers that project to the superficial gray layer. We have used both nitric oxide synthase inhibition (nw-nitro-L-arginine, NoArg) and single (nNOS) and double (nNOS and eNOS) gene knockout mice to examine the effect that reduction in NOS has upon the development of these two systems. The onset of NOS expression in rat, as revealed by nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) labeling, occurred in igl cells as early as postnatal day P5, with clusters being well-established by P14. Cholinergic fibers were first visible at P10 and formed obvious patches and tiers by P14. Intraperitoneal injections of NoArg from P1-P22 had no effect upon the development of these cholinergic patches. The pathway also developed normally in both single and double-knockout mice. In contrast, the ipsilateral retinocollicular pathway was altered in the double, but not in the single knockout mouse. This pathway is exuberant during the first week of life, being distributed across much of the mediolateral axis of the rostral SC. By P8-P15, this pathway has retracted to the most mediorostral SC. This refinement was delayed substantially in the double NOS gene knockout mouse. Ipsilateral fibers were found within 3-5 separate medio-lateral patches within the rostral 600 microns of SC at P15, and patches of abnormal size and extent were also seen at P18. We conclude from these results that NO plays a role in pathway development in the rodent SC, but only in glutamatergic pathways and only when both endothelial and neuronal forms of NOS have been deleted. The mechanism of this effect must involve pathway elimination in situations where there is non-correlated electrical activity. It is likely that NO promotes fiber retraction rather than fiber stabilization in these developing nerve fibers.
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PMID:The role of nitric oxide in development of the patch-cluster system and retinocollicular pathways in the rodent superior colliculus. 993 39

The present study has demonstrated the induction of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) reactivity and nitric oxide synthase-like immunoreactivity (NOS-LI) in the ventral horn motoneurons of the spinal cord in rats subjected to a single or multiple underground, or a single surface blast. Both enzyme activities were first detected in some motoneurons in laminae VIII and IX of Rexed, 3 hours after the blast. Some NADPH-d and NOS-LI positive neurons were also distributed in laminae VI and VII. The number and intensity of the labelled cells appeared to increase progressively, peaking at 2-3 days after the blast but were drastically reduced thereafter, so that at 7 days after the blast only a few positive neurons were observed. In rats killed at 2 weeks and in longer surviving intervals, i.e. up to 1 month, NADPH-d/NOS reactivity in the ventral horn motor neurons had diminished. The functional significance of the transient expression of neuronal NADPH-d/NOS after the blasts remains uncertain, although from a speculative point of view, the induction of these enzymes probably would reflect an increased production of nitric oxide (NO). In view of the lack of atrophic changes in most, if not all, of motor neurons, it is suggested that the increased levels of NO production after the blast injury may be involved in a neuroprotective function.
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PMID:Induction of NADPH diaphorase/nitric oxide synthase in the spinal cord motor neurons of rats following a single and multiple non-penetrative blasts. 1021 2

This study examined the occurrence of endothelial nitric oxide (NO)-synthase (NOS-III) in terminal mesenteric vessels and the involvement of NO in microvascular permeability. Possible effects were studied in bradykinin (BK)-induced and basal conditions. NOS expression was investigated by using NOS-III immunohistochemistry and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry on the light- and electron-microscopic levels. Permeability was examined in dissected mesenteries of male rats weighing 250-300 g. Tissue treatment was performed with BK (100 nM), sodium nitroprusside (SNP, 1 and 10 microM), L-nitroarginine (L-NA, 300 microM), BK and L-NA, BK and SNP, L-NA and SNP, as well as with BK, SNP (10 microM), and the guanylylcyclase inhibitor ODQ (10 microM), and BK and ODQ alone. Pharmacologically induced permeability changes were studied with fluorescein isothiocyanate (FITC)-dextran 70 kDa as a tracer for macromolecular transport. Video images were analyzed with computer determination of integrated optical density (IOI). Results were statistically verified by analysis of variance and t test. Microvascular permeability was increased by 168% after BK treatment and was enhanced by NO-synthesis inhibition with L-NA by 607%. However, the NO donor SNP led to a reduced tracer extravasation to 105 and 58%, respectively, an effect blocked by ODQ. Under basal conditions without prior BK induction, L-NA also causes an increase of IOI by 25%, whereas coapplication with SNP resulted in only a 10% increase of permeability. These results point out that NO has a modulatory role for microvascular permeability by supporting the barrier function of the endothelial lining in stimulated and nonstimulated conditions.
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PMID:Nitric oxide decreases microvascular permeability in bradykinin stimulated and nonstimulated conditions. 1036 98

Male rat copulatory ability decreases dramatically following castration. This may be due in part to the impairment of medial preoptic area (MPOA) dopamine (DA) release. Previous studies showed that extracellular DA levels in the MPOA of castrates were lower than in intact males, both during basal conditions and in the presence of a receptive female. However, tissue levels of DA in the MPOA were higher in castrates than in intact males, suggesting that DA synthesis may be normal or increased in castrates, but that release may be compromised. The current study found that neither long term (2 months) nor short term (2 weeks) castration had any effect on the number of neurons in the DA A(14) area that were immunoreactive (ir) for tyrosine hydroxylase (TH), the rate limiting enzyme for DA synthesis. Therefore, castration may not affect DA synthesis in the MPOA. Tissue levels of neurotransmitter reflect release, as well as synthesis. We previously reported that nitric oxide (NO) may increase DA release in the MPOA. The present study tested whether castration affected the number of NO producing cells in the MPOA. Long term, but not short term, castration significantly decreased the number of NADPH-d (nicotinamide adenine dinucleotide phosphate diaphorase) positive neurons and brain nitric oxide synthase immunoreactive (bNOS-ir) neurons in the medial preoptic nucleus (MPN). This suggests that in gonadally intact animals testosterone may activate NOS, which increases the production of NO. Long or short term castration had no effect on the numbers of bNOS-ir neurons in the paraventricular nucleus (PVN) or medial amygdala. However, short term castration decreased bNOS-ir neurons in the bed nucleus of stria terminalis (BNST). Thus, one means by which testosterone promotes male sexual behavior may be by increasing production of NO in the MPOA, which increases local DA release.
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PMID:Effects of testosterone on neuronal nitric oxide synthase and tyrosine hydroxylase. 1041 8

Nitric oxide (NO) is a unique biological messenger molecule. It serves, in part, as a neurotransmitter in the central and peripheral nervous systems. Neurons containing NO have been identified histochemically by the presence of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) reactivity or immunohistochemically by the antibody for neuronal NO synthase (n-NOS). Previous histochemical or pharmacological studies have raised the possibility that NO may play an important role in the neural pathways of the lower urinary tract. There is also considerable evidence to suggest that n-NOS is plastic and could be upregulated following certain lesions in the lower urinary tract. The present review summarises the distribution of n-NOS containing neurons innervating the urinary bladder and the changes of the enzyme expression in some experimentally induced pathological conditions.
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PMID:Neuronal nitric oxide synthase in the neural pathways of the urinary bladder. 1044 17

The purpose of this study was to determine whether nitric oxide (NO) is present in clinically normal horses under basal conditions and if it increases secondary to naturally acquired small intestinal strangulation obstruction. Thirty-one horses were used; 20 horses with naturally acquired small intestinal strangulation obstruction and 11 clinically normal horses with no signs of gastrointestinal tract disease. Jugular venous blood, abdominal fluid, and urine were collected for NO quantification. Plasma, abdominal fluid, and urine were stored at -70 degrees C until analyzed for NO using a chemiluminescent method. Biopsy specimens collected from the affected jejunal segment, during anesthesia or after immediately after euthanasia, or from the midjejunum of control horses, were divided into subsections for fixation in zinc formalin and cryopreservation in OCT gel. Nicotinamide adenine dinucleotide phosphate (reduced) (NADPH) diaphorase histochemical stains were performed on cryopreserved tissues and inducible nitric oxide synthase (iNOS) and nitrotyrosine immunohistochemical stains were performed on formalin-fixed, paraffin-embedded tissues. There were significantly greater plasma and abdominal fluid NO concentrations in affected horses as compared with controls, but there were no significant differences between horses for urine NO concentrations. There was a significant decrease in NADPH diaphorase stain in mucosal epithelium, vasculature, and leukocytes, and in submucosal plexi in affected horses compared with control horses. There was a significant increase in iNOS staining in mucosal and submucosal leukocytes and in mucosal leukocyte nitrotyrosine staining of the affected compared with control horses. Endothelial NOS and neuronal NOS are present under basal conditions in the jejunum of horses and probably mediate physiologic or cytoprotective effects. Plasma and abdominal fluid, but not urine, NO concentrations increase subsequent to small intestinal strangulation obstruction; this may be associated with increased mucosal and submucosal iNOS staining in leukocytes, which was likely due to increased expression subsequent to stimuli associated with ischemia. The increased nitrotyrosine staining in mucosal leukocytes of affected horses likely reflects the presence of peroxynitrite subsequent to increased NO and superoxide production and may reflect a cytotoxic role of NO in small intestinal strangulation obstruction in horses.
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PMID:Detection and comparison of nitric oxide in clinically normal horses and those with naturally acquired small intestinal strangulation obstruction. 1053 1

Nitric oxide (NO) may subserve different functions in different central neurons subjected to axotomy. The difference may depend on whether the neurons basally express neuronal nitric oxide synthase (nNOS), a biosynthetic enzyme of NO. This is supported by our previous finding that suggests the differential role of NO in neurons of nucleus dorsalis (ND) and red nucleus (RN) which have different basal expression of nNOS. This study aimed to establish firmly the functions of NO, as revealed by nNOS immunoreactivity and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry, by the administration of endogenous NO donor, l-arginine (l-arg), and NOS inhibitor, l-N(G)-nitroarginine methyl ester (l-NAME). To relate the role of NO to glutamate receptors (GluR), the distributions of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and N-methyl-d-aspartate receptor (NMDAR) in the two nuclei were revealed by immunohistochemical techniques. nNOS immunoreactivity was void in ND neurons, but expressed weakly in the RN normally. It was induced in ipsilateral ND neurons and upregulated on both sides of RN after spinal cord hemisection. Neuronal loss in the ipsilateral ND was augmented by l-arg, but reduced by l-NAME. In the contralateral RN, l-arg attenuated neuronal loss. NMDAR1 was present in most neurons in ND. After axotomy, some NMDAR1 immunoreactive neurons of the ipsilateral ND were induced to express NOS, whereas RN neurons showed strong staining for NMDAR1 and all the AMPA subunits. Most of the NOS-positive neurons in the RN were coexistent with GluR2 in normal rats and those subjected to axotomy. The present data demonstrated that NO exerted neurodestructive function in the non-NOS-containing ND neurons characterized by NMDAR as the predominant glutamate receptor. NO might be beneficial to the NOS-containing RN neurons. This could be attributed to the presence of GluR2. Possible diverse synthesizing pathways of NO in two different central nuclei were suggested from the observation that NOS was colocalized with NADPH-d in ND neurons, but not in RN neurons.
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PMID:Neuroprotective and neurodestructive functions of nitric oxide after spinal cord hemisection. 1068 69

It has been postulated that a segment (residues 594-645) inserted in the FMN subdomain of human endothelial nitric-oxide synthase (eNOS) plays a crucial role in controlling Ca(2+)-dependent CaM binding for eNOS activity. To investigate its functions, we expressed human eNOS in a baculovirus system with deletion of a 45-residue segment from this region (residues 594-606 and 614-645, designated as Delta45eNOS), and characterized the purified mutant enzyme. In contrast with wild-type eNOS, Delta45eNOS exhibited characteristics resembling inducible NOS (iNOS). It contained an endogenously bound CaM, which was essential in folding and stabilizing this mutant enzyme, and retained 60% of L-citrulline formation in 5 mM EGTA. We also produced four N-terminally truncated reductase domains with or without the 45-residue segment, and either including or excluding the CaM-binding sequence. Basal cytochrome c reductase activity of reductase domains without the 45-residue segment was up to 20 fold greater than that of corresponding insert-containing domains, and higher than CaM-stimulated activity of the wild-type enzyme. A series of mutants with smaller fragment deletion in this region such as Delta594-604, Delta605-612, Delta613-625, Delta626-634, Delta632-639, and Delta640-645 mutants were further characterized. The crude lysate of mutants Delta613-625 and Delta632-639 did not show activity in the presence of Ca(2+)/CaM, while other four mutants had activity comparable to that of WTeNOS. The purified Delta594-604 and Delta605-612 proteins had a 3-5-fold higher affinity for Ca(2+)/CaM, but their L-citrulline forming activity was still 80% dependent upon the addition of Ca(2+)/CaM. Both mutants exhibited a low level of the cytochrome c and ferricyanide reductase activities, which either did not respond to (Delta594-604) or slightly enhanced by (Delta605-612) the exogenous CaM. In contrast, activities of Delta626-634 and Delta640-645 like those of WTeNOS were largely Ca(2+)/CaM-dependent. Thus, our findings indicate that the N-terminal half of the 594-645 segment containing residues 594-612 plays a significant role in regulating Ca(2+)/CaM binding.
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PMID:Characterization of the roles of the 594-645 region in human endothelial nitric-oxide synthase in regulating calmodulin binding and electron transfer. 1077 22


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