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)

Canine narcolepsy is a unique experimental model of a human sleep disorder characterized by excessive daytime sleepiness and cataplexy. There is a consensus recognition of an imbalance between cholinergic and catecholaminergic systems in narcolepsy although the underlying mechanisms remain poorly understood. Possible substrates could be an abnormal organization, numbers and/or ratio of cholinergic to catecholaminergic cells in the brain of narcoleptic dogs. Therefore, we sought to characterize the corresponding neuronal populations in normal and narcoleptic dogs (Doberman Pinscher) by using choline acetyltransferase (ChAT), nicotinamide adenosine dinucleotide phosphate (NADPH)-diaphorase, tyrosine hydroxylase (TH), and dopamine beta-hydroxylase (DBH). Cholinergic cell groups were found in an area extending from the central to the gigantocellular tegmental field and the periventricular gray corresponding to the pedunculopontine tegmental nucleus (PPT), the laterodorsal tegmental nucleus (LDT), and the parabrachial nucleus. An almost perfect co-localization of ChAT and NADPH-diaphorase was also observed. Catecholaminergic cell groups detected included the ventral tegmental area, the substantia nigra, and the locus coeruleus nucleus (LC). The anatomical distribution of catecholaminergic neurons was unusual in the dog in two important aspects: i) TH- and/or DBH-immunoreactive neurons of the LC were found almost exclusively in the reticular formation and not within the periventricular gray, ii) very few, if any TH-positive neurons were found in the central gray and dorsal raphe. Quantitative analysis did not reveal any significant differences in the organization and the number of cells identified in the LDT, PPT, and LC of normal and narcoleptic dogs. Moreover, the cholinergic to catecholaminergic ratio was found identical in the two groups. In conclusion, the present results do not support the hypothesis that the neurochemical imbalance in narcolepsy could result from abnormal organization, numbers, or ratio of the corresponding neuronal populations.
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PMID:Mesopontine organization of cholinergic and catecholaminergic cell groups in the normal and narcoleptic dog. 905 Jul 84

The ventrolateral medulla, including the A1 and C1 catecholamine cell groups, corresponds to the recently defined ventrolateral intermediate reticular zone (IRt) in humans. We sought to determine whether the distribution of neuropeptide Y (NPY) corresponds to that of subpopulations of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) reactive neurons in human ventrolateral IRt. Medullae obtained from 2 men (ages 69 and 59, no history of neurologic disease, postmortem delay 22 and 5 h, respectively) were processed for NPY, tyrosine hydroxylase (TH) and NADPH-d either alone or combining NADPH-d and NPY or NADPH-d and TH, respectively. Distribution of cells was plotted using computer-aided reconstruction. NPY-reactive neurons were found throughout the rostrocaudal extent of the ventrolateral IRt, particularly at mid-olivary levels. The distribution of NPY immunoreactivity overlapped TH but not NADPH-d reactivity. This indicates that NPY and NADPH-d reactivity may help identify different subpopulations of neurons in human ventrolateral IRt, which may be differentially susceptible to disease.
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PMID:Distribution and relationships of neuropeptide Y and NADPH-diaphorase in human ventrolateral medulla oblongata. 905 21

To reveal neurones in the cat medulla oblongata involved in carotid baroreceptor/chemoreceptor reflexes, the distribution of c-Fos oncoprotein immunoreactivity was studied following electrical stimulation of the right carotid sinus nerve. The neurochemistry of the activated neurones was investigated using antisera to tyrosine hydroxylase, neuropeptide Y, somatostatin, and glutamate. Nitric oxide containing neurones were identified using antiserum to nitric oxide synthase (NOS) and by the histochemical localization of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase. Following sinus nerve stimulation numerous c-Fos-IR cells were detected both ipsilaterally and contralaterally in the nucleus tractus solitarii, the area postrema and throughout the ventrolateral medulla. Dual labelling studies revealed that 3.3% of c-Fos-immunoreactive cells in the nucleus tractus solitarii were also immunoreactive for tyrosine hydroxylase. The double labelled cells were scattered within the medial and ventrolateral subnuclei, predominantly rostral to obex. A higher proportion (10.3%) of c-Fos-IR cells in the ventrolateral medulla also showed tyrosine hydroxylase immunoreactivity. Caudal to obex, these were scattered in the reticular formation between the spinal trigeminal nucleus and the lateral reticular nucleus, while more rostrally they were found within the lateral reticular nucleus, the nucleus ambiguus and the lateral tegmental field. Cells expressing c-fos and reactive for glutamate, neuropeptide Y or NADPH-diaphorase (or NOS) were only rarely seen, and co-localization of c-Fos and somatostatin immunoreactivities was not seen. These results suggest that of the neurones forming pathways within the medulla activated on carotid sinus nerve stimulation, presumably mediating baro- and chemoreceptor reflexes, relatively few utilize catecholamines, glutamate, neuropeptide Y or nitric oxide as their transmitter substance.
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PMID:Co-localization of c-Fos and neurotransmitter immunoreactivities in the cat brain stem after carotid sinus nerve stimulation. 931 68

In this study, we assessed the effects of normal ageing on the number, distribution, and somal area of nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd)-positive (NADPHd+) and tyrosine hydroxylase-immunoreactive (TH-IR) amacrine cells in human and rat retina. By using a double-labelling immunohistochemical technique, we have shown that these two enzymes are located in separate amacrine cell populations in the human retina. In normal human retinas from organ donors, we have shown that there was no change in the number, somal area, or retinal distribution of NADPHd+ neurons over an age range of 19-89 years. In contrast, there was a significant decrease (P < 0.05) of 52% in the total number of TH-IR neurons in the group aged 65-89 years compared with the group aged 19-64 years. CA1 and CA2 TH-IR neurons were reduced by 44% and 55%, respectively. In young (3 months) and old (2 years) rats, the number of NADPHd+ neurons did not decrease with ageing, but the number of TH-IR neurons was significantly reduced by 21% (P < 0.05). In a companion study on monkey retina, we have shown that a postmortem delay of 12.5 hours between death and fixation results in a decrease of 33% in the number of both NADPHd+ and TH-IR neurons in the retina compared with the number in retinas fixed immediately after death. The findings of this study on the two subsets of amacrine cells, therefore, are likely to demonstrate the consequences of ageing in the retina and might contribute to visual impairment in the elderly.
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PMID:Ageing has a differential effect on nitric oxide synthase-containing and catecholaminergic amacrine cells in the human and rat retina. 941 25

Adaptation of the skin colour to the background light condition in the amphibian Xenopus laevis is achieved by migration of pigment granules in the skin melanophores, a process regulated by alpha-MSH secretion from melanotrope cells in the pituitary pars intermedia (PI). alpha-MSH secretion in turn, is regulated by various stimulatory and inhibitory messengers synthesized in brain nuclei, especially the hypothalamic suprachiasmatic and magnocellular nuclei and the locus coeruleus in the hindbrain. In the present study, the roles in background adaptation of nitric oxide (NO) and NO synthase (NOS) enzyme activity were evaluated. In situ, using both immunohistochemistry with anti-human brain NOS (bNOS) serum in paraffin-embedded material and using nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry in cryo-sections, we showed NOS in neurons in the optic tectum and in the locus coeruleus. NADPH-d reactivity was also found in neurons in the lateral amygdala, the ventral hypothalamic nucleus and in fibers in the median eminence. Using a Western blot stained with an anti-human bNOS serum, we demonstrated a 150 kDa band in Xenopus hindbrain lysates, which is similar to the NOS protein present in the rat anterior pituitary, but which was not detectable in the lysates from both the neurointermediate and distal lobes in Xenopus. No differences in histochemical staining pattern or on Western blotting were observed between animals adapted to a black or a white background. Paraffin sections of the endocrine PI and pars distalis did not reveal bNOS-like immunoreactivity. NADPH-d reactivity was observed in the endothelia of this gland. However, using a new procedure of thin cryo-sections of pituitary neurointermediate lobes, we observed bNOS-immunoreactive fibers as well as cyclic 3',5' guanosine monophosphate (cGMP)-accumulating fibers in the PI. The PI may be regulated by NOergic neurons from higher brain centers. The possibility that NOergic neurons in the locus coeruleus are involved in the innervation of the PI needs further investigation. The latter neurons are probably not noradrenergic because double labeling studies show no co-localization of NADPH-d reactivity and tyrosine hydroxylase immunoreactivity in locus coeruleus neurons.
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PMID:Nitric oxide synthase and background adaptation in Xenopus laevis. 949 64

Recent studies dealing with the investigation of the afferent and efferent connections of the basal ganglia of amphibians have revealed many similarities with basal ganglia structures of amniotes. In a further step, the chemoarchitecture of basal ganglia of the frog Rana perezi has been investigated. For use as main markers of amphibian basal ganglia structures, antibodies against tyrosine hydroxylase, substance P, and enkephalin were selected. Moreover, the distributions of nitric oxide synthase (nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry), calretinin, dopamine-beta-hydroxylase, choline acetyltransferase, mesotocin, vasotocin, somatostatin, neuropeptide Y, neuropeptide FF, and serotonin were studied to corroborate a comparison with both basal ganglia and amygdaloid structures of amniotes. On the basis of connections and chemoarchitecture, a striatum proper, nucleus accumbens, dorsal and ventral pallidum, bed nucleus of the stria terminalis, and amygdaloid complex have been identified. Accordingly, a new terminology is proposed that is in line with our current understanding of basal ganglia organization in amphibians.
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PMID:Basal ganglia organization in amphibians: chemoarchitecture. 951 19

Enteric neurons have distinct neurochemical codings in each species. The basal tone of the gastrointestinal tract of the rabbit is low and produces neurally evoked pendular movements. Therefore, it might have an innervation pattern different from that of other laboratory animals. We have characterised myenteric neuron populations in rabbit ileum with neurochemical markers that are known to be associated with distinct cell types and/or fibre systems in the myenteric plexus. The density of nerve cells estimated with the NADH-diaphorase technique was about 2500 cells/cm2 and most, if not all, neurons contained microtubule-associated protein 2. NADPH-diaphorase-positive cells were numerous. One cell type was large and emitted long straight processes, whereas small cells bore thin filamentous dendrites. Neurons immunoreactive for 28-kDa calcium-binding protein were rare. Over 70% of them had very strongly labelled lamellar dendrites. Their axons were beaded and formed pericellular baskets around unstained somata. We found very few small tyrosine-hydroxylase-positive cells. The fibre network in the plexus was very strong; the axons formed many pericellular baskets. In double labelling studies, no co-localisation was revealed between the 28-kDa calcium-binding protein and NADPH-diaphorase. Some fibres containing 28-kDa calcium-binding protein formed only a few contacts on somata of NADPH-diaphorase-positive cells. None of the NADPH-diaphorase-labelled cells were found to be stained for tyrosine hydroxylase. Tyrosine-hydroxylase-positive fibres rarely made pericellular baskets on the surface of NADPH-diaphorase-positive somata. Strongly immunolabelled pericellular baskets were never observed around NADPH-diaphorase-positive cell somata. The results suggest that myenteric neurons in rabbit comprise distinct and characteristic neurochemical properties that are different from the rodent pattern. Therefore, the explanation of the motility pattern of rabbit intestine can be approached on a chemical neuroanatomical basis.
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PMID:Some neurohistochemical properties of nerve elements in myenteric plexus of rabbit ileum: similarities and dissimilarities to the rodent pattern. 956 Apr 71

The distribution of nitrergic neurons was investigated by using nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry and nitric oxide synthase (NOS) immunohistochemistry in wholemount preparations of the urinary bladder in guinea pigs. Both NADPH-d+ and NOS+ neurons were located predominantly in the bladder base. Double staining showed that 70.9% of the NADPH-d+ neurons coexpressed NOS. Acetylcholinesterase histochemistry revealed that a majority of the intramural neurons were reactive, and about half of them (51.4%) were double labelled for NOS. Tyrosine hydroxylase-positive neurons were also distributed mainly in the bladder base but in a neuronal population that was separate from the preponderant NADPH-d+ neurons. Vasoactive intestinal polypeptide immunoreactivity was also detected in the some of intramural ganglion cells, in which 21.3% of them coexpressed NADPH-d. Calcitonin gene-related peptide and substance P immunoreactivities were confined to nerve fibers, often in close association with NADPH-d+ cells or extended along the blood vessels. These results have demonstrated the colocalization of NADPH-d and NOS in the majority of intramural ganglion cells. Many of the nitrergic neurons are apparently cholinergic, indicating that they are parasympathetic postganglionic neurons, and this underscores NO as the major neuromodulator in the parasympathetic nerves in the bladder walls. The localization of vasoactive intestinal polypeptide in nitrergic neurons suggests that the peptide may complement NO for regulation of micturition reflex. The close relationship of NADPH-d-reactive intramural neurons with calcitonin gene-related peptide and substance P fibers, most probably derived from dorsal root ganglion cells, suggests that NO released from the local neurons may exert its influence on the sensory neural pathways in the urinary bladder.
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PMID:Colocalization of nitric oxide synthase and some neurotransmitters in the intramural ganglia of the guinea pig urinary bladder. 959 May 57

The objective of the present study was to investigate the potential role of the free radical nitric oxide (NO) in the development of fetal rat mesencephalic neurons grafted in a 6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson's disease. First, using nitric oxide synthase (NOS)-immunocytochemistry and reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry, we investigated the presence of the neuronal isoform of NOS (nNOS) in intrastriatal mesencephalic grafts. During the course of the experiment (16 weeks) an increase in the staining intensity and the number of nNOS/NADPH-d positive cells within the grafts was observed, as well as a gradual maturation of dopaminergic neurons. In addition, within both the host striatal and grafted mesencephalic tissue, a NO-dependent accumulation of cyclic guanosine monophosphate (cGMP) was detected, indicating the presence of guanylate cyclase, i.e., the target-enzyme for NO. Secondly, to determine the impact of NO on the survival of grafted dopaminergic neurons, 6-OHDA lesioned rats received mesencephalic grafts and were subsequently treated with the competitive NOS-inhibitor Nomega-nitro-l-arginine methylester (l-NAME). After chronic treatment for 4 weeks, tyrosine hydroxylase immunocytochemistry revealed no apparent differences between the survival of grafted dopaminergic neurons in control- or l-NAME treated animals, respectively. As the maturation of grafted dopaminergic neurons coincides with a gradual increase in the expression of nNOS within the graft and since dopaminergic cell numbers are not changed upon administration of l-NAME, it is concluded that endogenously produced and potentially toxic NO does not affect the survival of grafted fetal dopaminergic neurons.
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PMID:Sustained pharmacological inhibition of nitric oxide synthase does not affect the survival of intrastriatal rat fetal mesencephalic transplants. 959 18

The expression of nitric oxide synthase (NOS) in the olfactory bulb was compared between two mouse strains, CD-1 and BALB/c, that differ in the connectivity within their olfactory glomeruli, their content of tyrosine hydroxylase, and their response to olfactory deafferentation. Labelled cells were qualitatively and quantitatively analyzed by both immunohistochemistry for NOS and histochemistry for nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase (ND). Both periglomerular cells and short-axon cells were observed with both techniques employed, and their colocalization in the same neurons demonstrated that ND is a reliable marker for NOS-expressing cells in the mouse olfactory bulb (OB). The histochemical technique differentiates two types of glomeruli: ND-positive and ND-negative. Olfactory glomeruli in the CD-1 strain were about 7% larger than those in the BALB/c animals. While the density of NOS/ND-containing periglomerular cells was similar between both strains studied, more NOS/ND-labelled cells were observed in the ND-positive glomeruli (P = 0.002). Since periglomerular cells in the BALB/c strain do not receive direct olfactory receptors synapses, the present results indicate that such inputs do not regulate the expression of NOS and ND activity in the periglomerular cells. The different densities of NOS/ND-expressing periglomerular cells may indicate that nitric oxide is implicated in a differential modulation of the odor response within both types of chemically distinct glomeruli in the mouse olfactory bulb.
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PMID:NADPH-diaphorase histochemistry reveals heterogeneity in the distribution of nitric oxide synthase-expressing interneurons between olfactory glomeruli in two mouse strains. 967 81


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