Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The motility of the avian cloaca is under neural control, but little is known about the neural network that accomplishes this function. This present study was designed to determine the distribution of nitric oxide-synthesising neurons in the pigeon cloaca by enzyme histochemistry for reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d). NADPH-d-positive staining was seen in the neurons and fibres in the cloaca. The highest density of nerve fibres was noted in the coprodeum and the lowest in the proctodeum. In the coprodeum, NADPH-d neurons were found singly, formed small groups of 2-10 neurons, or were seen in plexuses in the muscle layer, lamina propria, or around the arterioles. Several NADPH-d-positive neurons were also observed in the ganglia of the cloaca. NADPH-d fibres ran in the muscle layer, lamina muscularis mucosae and lamina propria, or surrounded blood vessels. The distribution pattern of acetylcholinesterase (AChE)-stained neurons and fibres in the cloaca was similar to that of NADPH-d. Double staining for NADPH-d and AChE showed colocalisation of the 2 enzymes in many neurons of the cloaca. Tyrosine hydroxylase (TH)-immunoreactive nerve fibres originating outside the cloaca were also noted. In the urodeum and proctodeum, neurons or fibres positive for NADPH-d, AChE or TH were scattered in the lamina propria. Nerve fibres immunoreactive for calcitonin-gene related peptide, galanin, methionine-enkephalin, substance P, and vasoactive intestinal peptide were found sparsely in the cloaca. Our results demonstrate that nitrergic neurons constitute a subpopulation which is closely associated with the cholinergic system in the pigeon cloaca.
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PMID:Innervation of NADPH diaphorase-containing neurons correlated with acetylcholinesterase, tyrosine hydroxylase, and neuropeptides in the pigeon cloaca. 1127 43

The role of cytochrome P450 (CYP) and the CYP isoform involved in the activation of the widely used pesticide methyl-parathion (MePA) were investigated in rat brain extracts by measuring the effect of different CYP inhibitors on acetylcholinesterase (AChE) inhibition by MePA. Brain extracts provide a useful tool to study the activation mechanisms of organophosphorus compounds (OP) since they contain both the activating enzyme(s) and the molecular target for OP toxicity. As expected, in incubations of rat brain extract supplemented with NADPH, AChE activity was non-competitively inhibited by the presence of MePA, indicating that MePA was activated to its reactive metabolite methyl-paraoxon (MePO). Indeed, Vmax(app) decreased from 13.4 to 8.7 micromol thionitrobenzoic acid (TNB)/min per mg protein. MePA activation by rat brain extracts, as measured by the AChE inhibition produced by the presence of the pesticide in the incubation, was fully prevented by previously bubbling the incubation mix with CO, by the presence of monoclonal anti-rat CYP2B1/2B2 antibodies and by the addition of phenobarbital (PB), a CYP2B substrate. Interestingly, MePA showed a greater affinity for CYP2B than PB. CYP1A1 antibodies showed no effect on MePA activation. The presence of cytochrome P450 2B (CYP2B) in the rat brain extracts was confirmed by immunoblotting. These results demonstrate indisputably the responsibility of CYP2B in MePA activation in the rat brain in vitro, suggesting that metabolic activation of OP compounds in situ might be crucial for their organ specific toxicity to the central nervous system also in vivo.
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PMID:Cytochrome P450 2B (CYP2B)-mediated activation of methyl-parathion in rat brain extracts. 1168 53

Calbindin-D(28k) (CB), calretinin (CRT), and parvalbumin (PV) are high-affinity cytosolic calcium (Ca(2+)) binding proteins (CBP) that have been found to regulate intracellular calcium concentrations in neurons through their buffering capacity and to protect neurons from insults that induce elevations of intracellular Ca(2+). In earlier studies we observed a substantial and neurochemically specific loss of CB from the human basal forebrain cholinergic neurons (BFCN) in the course of normal aging. In the present experiments we expanded our investigation of age-related changes in calcium binding proteins in the human brain by investigating the status of CB-, CRT-, and PV-positive neurons in 17 cortical areas. There was a trend toward a decrease in the number of CB-immunoreactive neurons in all areas studied. However, this trend reached significance in only 4 areas in which the loss of CB-positive neurons ranged between 20 and 46%. Immunoreactivity for CRT was also decreased in many areas and this difference reached significance in three regions (26-37%). Cortical neurons displaying PV immunoreactivity did not show an age-related change. Comparison with other neurochemically specific cortical neurons indicated a similar age-related loss of nonphosphorylated neurofilament and NADPH-d activity in only a few cortical areas. In contrast, neuronal acetylcholinesterase activity was increased in a few cortical areas. These observations indicate that loss of CBP-positive neurons occurs in restricted cortical regions and is not a specific change as other neurochemically specific neurons also display restricted age-related changes. Furthermore, the age-related changes in cortical CBP-positive neurons appear to be considerably smaller than similar changes in the BFCN. The age-related depletion of CBPs is likely to deprive neurons from the capacity to buffer intracellular calcium and thus to leave them vulnerable to pathological processes that can cause increased intracellular calcium and lead to their degeneration.
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PMID:Age-related changes in calbindin-D28k, calretinin, and parvalbumin-immunoreactive neurons in the human cerebral cortex. 1282 92

Changes in the distribution of NADPH-diaphorase (NADPH-d) and acetylcholinesterase (AChE) were studied in neurons of the stellate ganglion in newborn, 10-, 20-day-old, 1-, 2-, 4- and 6-month-old kittens. AChE-positive neurons were revealed in the stellate ganglion (SG) from birth onwards. The number of these neurons increased until 20 days of postnatal life and then declined in 1- and 2-month-old kittens. A small number of weakly stained, NADPH-d-positive cells were found in newborn kittens, while intensely stained neurons first appeared in 10-day-old animals and increased in number up to the second month of life. The size of AChE-positive neurons was larger in comparison with NADPH-d-positive cells in the stellate ganglion of all animals under study. We suggest that putative vasodilator neurons or cells innervating sweat glands exhibit different development patterns from the moment of birth.
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PMID:Histochemical features of neurons in the cat stellate ganglion during postnatal ontogenesis. 1287 76

Human lymphocytes were exposed to the leukemogenic pesticide isofenphos (IFP) to investigate its effects on chromosomal DNA and cholinergic homeostasis using cholinesterase activity as a marker. Isolated peripheral lymphocytes were administered concentrations of IFP ranging from 0.1 ng/ml to 10 microg/ml. The absence (Group 1) and presence (Group 2) of DNA repair inhibitors 4 mM hydroxyurea (HU), 40 microM cytosine arabinoside (ARA-C) and an NADPH regenerating system (NRS) (Group 3) were analyzed at 1, 6 and 24 h by single cell gel electrophoresis using the comet assay. Significant damage to DNA directly from IFP at 1 h by remarkably low concentrations was observed in Group 1, escalating in Group 2 with DNA repair inhibition, while Group 3 disruptions were highest due to the presence of the NRS P-450 microsomal fraction conducive to producing reactive IFP-oxon and N-desalkyl metabolites. The extent of DNA aberrations increased further in parallel within the groups at 6 and 24 h. Male and female chemical sensitivities were similar on average (P < 0.01). Cholinesterase activity measured in a satellite group was inhibited with 0.1 microg/ml IFP by 69, 62, and 48% at 1, 6, and 24 h, respectively, indicating gradual induction of compensatory synthesis. Restoration of cholinergic homeostasis may be exceptionally impaired at higher IFP concentrations from acetyl-CoA depletion [Leuk. Res. 25 (2001) 883]. In summary, these studies reveal that exposure to the organophosphate pesticide isofenphos induces human DNA mutation beyond endogenous repair capacity and disrupts cholinergic nuclear signaling affectively constructing the mutator phenotype of leukemogenesis.
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PMID:Chromosomal aberrations in human lymphocytes exposed to the anticholinesterase pesticide isofenphos with mechanisms of leukemogenesis. 1523 72

Tacrine, a cholinesterase inhibitor, was approved for the treatment of Alzheimer's disease. Oxidative metabolism of tacrine occurs by CYP1A-catalyzed hydroxylation. In rats, it was observed that the area under the curve (AUC) of the second oral dose was consistently higher than the AUC after the first oral dose, which was not due to the accumulation of the drug in the plasma from the first dose. This finding suggested inhibition of the enzyme during metabolism or inhibition by a metabolite. The inhibitory mechanism was studied in liver and intestinal microsomes prepared from 3-methylcholanthrene-treated rats and with recombinant CYP1A1 and CYP1A2. Preincubation of CYP1A2 with tacrine and NADPH revealed a time-dependent inhibition of 7-ethoxyresorufin O-de-ethylation with a K(i) of 1.94 microM and a k(inact) of 0.091 min(-1). No time-dependent inhibition was observed with CYP1A1 or with 1-hydroxytacrine or 2-hydroxytacrine. Tacrine metabolism catalyzed by CYP1A was also carried out, and the partition ratio was estimated to be 22. A modified Michaelis-Menten equation involving mechanism-based inhibition was derived and used to analyze the data. Reasonable parameter fits were obtained indicating that this equation is suitable to describe metabolism data when the substrate is a mechanism-based inhibitor of the enzyme. The probable inactivation mechanism involves either hydrogen atom abstraction to produce a carbon-centered radical intermediate at the benzylic position or insertion of OH(+) into a C-H bond with subsequent loss of water to produce a carbocation. Rapid rearrangement of the carbocation or radical and subsequent covalent binding of the tacrine moiety would result in enzyme inactivation.
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PMID:Inhibition of murine cytochrome P4501A by tacrine: in vitro studies. 1525 5

The cyto- and chemoarchitecture of the anterior olfactory nucleus and piriform cortex of the short-beaked echidna and platypus were studied to determine: (1) if these areas contain chemically distinct subdivisions, and (2) if the chemoarchitecture of those cortical olfactory regions differs from therians. Nissl and myelin staining were applied in conjunction with enzyme reactivity for NADPH diaphorase and acetylcholinesterase, and immunoreactivity for calcium-binding proteins (parvalbumin, calbindin and calretinin) and tyrosine hydroxylase. Golgi impregnations were also available for the echidna. In the echidna, the anterior olfactory nucleus is negligible in extent and merges at very rostral levels with a four-layered piriform cortex. Several rostrocaudally running subregions of the echidna piriform lobe could be identified on the basis of Nissl staining and calcium-binding protein immunoreactivity. Laminar-specific differences in calcium-binding protein immunoreactivity and NADPH-d-reactive neuron distribution were also noted. Neuron types identified in echidna piriform cortex included pyramidal neurons predominating in layers II and III and non-pyramidal neurons (e.g., multipolar profusely spiny and neurogliaform cells) in deeper layers. Horizontal cells were identified in both superficial and deep layers. By contrast, the platypus had a distinct anterior olfactory nucleus and a three-layered piriform cortex with no evidence of chemically distinct subregions within the piriform cortex. Volume of the paleocortex of the echidna was comparable to prosimians of similar body weight and, in absolute volume, exceeded that for eutherian insectivores such as T. ecaudatus and E. europaeus. The piriform cortex of the echidna shows evidence of regional differentiation, which in turn suggests highly specialized olfactory function.
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PMID:The anterior olfactory nucleus and piriform cortex of the echidna and platypus. 1649 95

Indium nitrate is mainly used as a semiconductor in batteries, for plating and other chemical and medical applications. There is a lack of available information about the adverse effects of indium compounds on aquatic organisms. Therefore, the toxic effects on systems from four trophic levels of the aquatic ecosystem were investigated. Firstly, the bacterium Vibrio fischeri, the alga Chlorella vulgaris and the cladoceran Daphnia magna were used in the toxicological evaluation of indium nitrate. The most sensitive model was V. fischeri, with a NOAEL of 0.02 and an EC(50) of 0.04 mM at 15 min. Although indium nitrate should be classified as harmful to aquatic organisms, it is not expected to represent acute risk to the aquatic biota. Secondly, PLHC-1 fish cell line was employed to investigate the effects and mechanisms of toxicity. Although protein content, neutral red uptake, methylthiazol metabolization, lysosomal function and acetylcholinesterase activity were reduced in cells, stimulations were observed for metallothionein levels and succinate dehydrogenase and glucose-6-phosphate dehydrogenase activities. No changes were observed in ethoxyresorufin-O-deethylase activity. To clarify the main events in PLHC-1 cell death induced by indium nitrate, nine modulators were applied. They were related to oxidative stress (alpha-tocopherol succinate, mannitol and sodium benzoate), disruption of calcium homeostasis (BAPTA-AM and EGTA), thiol protection (1,4-dithiotreitol), iron chelation (deferoxiamine) or regulation of glutathione levels (2-oxothiazolidine-4-carboxylic acid and malic acid diethyl ester). The main morphological alterations were hydropic degeneration and loss of cells. At least, in partly, toxicity seems to be mediated by oxidative stress, and particularly by NADPH-dependent lipid peroxidation.
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PMID:Toxicological assessment of indium nitrate on aquatic organisms and investigation of the effects on the PLHC-1 fish cell line. 1780 41

Rectal suction biopsy (RSB) is the gold standard diagnostic procedure for disorders of bowel motility. This study describes our experience with RSB stained with histochemistry as the first diagnostic approach in a large series of patients presenting with chronic constipation. Between 1993 and 2005, 766 children underwent RSB for persistent chronic constipation. The specimens were snap frozen, sectioned and stained with conventional hematoxylin and eosin (H&E) and with nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) and acetylcholinesterase (AChE) histochemical stainings. Adequate amount of submucosa was present in 655 (85.5%) out of 766 cases and formed the basis of this study. RSB in 540 (82%) patients were reported as normal. Hirschsprung's disease was found in 47 (7.2%) patients with characteristic features of absence of ganglion cells, increased AChE activity in the lamina propria and muscularis mucosae, thick nerve fibers in the submucosa, and a lack of NADPH-d-positive fibers in muscularis mucosae. RSB in 59 (9%) patients presented features of intestinal neuronal dysplasia such as submucosal hyperganglionosis, giant ganglia, ectopic ganglia and increased AChE activity in lamina propria. Hypoganglionosis was suspected in nine (1.3%) children because of sparse or absent ganglion cells and low AChE and NAPDH-d activity in muscularis mucosae. Three patients (0.4%) developed bleeding following RSB, requiring diathermy of the bleeding point. Thus, we conclude that RSB is a simple and safe method when used as the first diagnostic approach in patients with chronic constipation. The combination of two histochemical stainings techniques provides a high level of accuracy in the diagnosis of intestinal dysganglionosis.
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PMID:Histochemical staining of rectal suction biopsies as the first investigation in patients with chronic constipation. 1846 82

The neuroanatomy of the ileocecal valve (ICV) is poorly understood. A better understanding of this important functional component of the gastrointestinal tract would enable surgeons to reconstruct an effective valve following surgical resection of the ICV. ICVs were examined in young pigs (N = 5) using frontal and transverse paraffin embedded and frozen sections. Hematoxylin+Eosin (H+E) staining, acetylcholinesterase (AchE), and NADPH-diaphorase (NADPH-d) histochemistry and protein gene product 9.5 (PGP 9.5) and C-kit immunohistochemistry were performed. The H+E staining revealed that the ICV consists of three muscle layers: an external circular muscle layer continuous with that of the ileal circular muscle layer, an inner circular muscle layer continuous with that of the cecal circular muscle layer, and a single longitudinal muscle layer, which appears to be secondary to a fusion of the ileal and cecal longitudinal muscle layers. The AchE, NADPH-d, and PGP 9.5 staining revealed two distinct coaxial myenteric plexuses, together with superficial and deep submucosal plexuses. The C-kit immunostaining showed a continuous myenteric ICC network within the ICV. The structure of the neuromuscular components within the ICV suggests that the valve is a result of a simple intussusception of the terminal ileum into the cecum. This knowledge may help surgeons in their future attempts at reconstructing more anatomically and functionally suitable ICVs following surgical resection of native ICVs.
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PMID:New insights into the neuromuscular anatomy of the ileocecal valve. 1908 3


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