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

Calcineurin, a multifunctional Ca2+ (divalent cations)-dependent calmodulin-stimulated phosphoprotein phosphatase, has been reported to be present in the striatal neurons which project to the globus pallidus and the substantia nigra. In the present study, we examined what types of cells in the rat striatum express calcineurin. The calcineurin-positive neurons were of medium size (mean diameter of 16 microns) and constituted about 60-70% of the total neuronal population in the striatum. Under light microscopy, the calcineurin-positive neurons had round, triangular, or polygonal cell bodies with a relatively small amount of cytoplasm. Electron microscopic examination of 20 randomly selected striatal calcineurin-immunoreactive neurons revealed that their nuclei did not show any invaginations or intranuclear inclusions. The calcineurin-positive neurons were characterized by Golgi impregnation as the densely spinous type. On the other hand, it was demonstrated that calcineurin-positive neurons are a separate population from the diisopropylfluorophosphate-acetylcholinesterase-positive cells or nicotinamide adenine dinucleotide phosphate diaphorase-positive cells, by means of the combination of immunocytochemistry and enzyme histochemistry. In addition, simultaneous localization of calcineurin and substance P in a single cell was observed in some striatal neurons using a double immunostaining method. On the basis of these findings, it was considered that most calcineurin-immunoreactive neurons in the rat striatum may be classified as medium-size densely spiny neurons.
 ...
PMID:Morphological characterization of the rat striatal neurons expressing calcineurin immunoreactivity. 244 61

1. The action of beryllium on the following enzymes has been examined: alkaline phosphatase (Escherichia coli and kidney), acid phosphatase, phosphoprotein phosphatase, apyrase (potato), adenosine triphosphatase (liver nuclei, liver mitochondria, brain microsomes), glucose 6-phosphatase, polysaccharide phosphorylases a and b, phosphoglucomutase, hexokinase, phosphoglyceromutase, ribonuclease, A-esterase (rabbit serum), cholinesterase (horse serum), chymotrypsin. Alkaline phosphatase and phosphoglucomutase are inhibited by 1mum-beryllium sulphate whereas the other enzymes are largely unaffected by 1mm-beryllium sulphate. 2. Possible mechanisms for the inhibition of phosphoglucomutase and alkaline phosphatase are discussed.
 ...
PMID:The inhibition of enzymes by beryllium. 428 87

In cultured human neuroblastoma cells (SK-N-MC), a plasma membrane-bound besides a lysosomal ganglioside GM3 sialidase was detected. Both activities can be distinguished by the specific activation with detergents, as well as differential inhibition by Cu++. Plasma membrane and lysosomal sialidase specific activities showed strikingly different behaviour during the growth phase of neuroblastoma cells. Thus, the plasma membrane sialidase increased about 15-fold and mirrored cell growth, it differed from the kinetics of ornithine decarboxylase, an early marker of cell proliferation. The lysosomal sialidase, on the other hand, exhibited constant specific activities during growth of the cells, as did lysosomal and plasma membrane marker enzymes. When the sialidase inhibitor 2,3-dehydro-2-deoxy-N-acetylneuraminic acid was included in the culture medium, a profound change in proliferation kinetics was observed, indicating a release from density-dependent control of cell division. Additionally, the inhibitor abolished the increase of the biochemical differentiation marker acetylcholinesterase. The results suggest an important role of the ganglioside sialidase of the plasma membrane in the processes of proliferation control and differentiation in this neuronal cell system.
 ...
PMID:Role of plasma membrane ganglioside sialidase of human neuroblastoma cells in growth control and differentiation. 814 59

Alzheimer's disease is a chronic neurodegenerative disorder that is characterized by memory impairment, cognitive dysfunction, behavioral disturbances, and deficits in activities of daily living. A consistent observation in these patients is that cholinergic neurons are affected and deteriorate over time, leading to decreased levels of acetylcholine (ACh). Acetylcholinesterase (AChE) inhibitors, which attempt to prevent the breakdown of ACh, may be classified as short acting, intermediate acting, and long acting based on AChE regeneration time. Metrifonate is converted by a nonenzymatic process to the long-acting cholinesterase inhibitor 2,2-dichlorovinyl dimethyl phosphate (DDVP). Acetylcholinesterase inhibition produced by metrifonate occurs rapidly, is dose dependent, can be detected by inhibition measured in red blood cells, and can be reversed by oxime administration. Metrifonate and DDVP improved performance in young rats; cognitive improvement in aged rats also was observed. Both agents were well tolerated and did not have significant effects on various preclinical pharmacologic safety tests.
 ...
PMID:Preclinical pharmacology of metrifonate. 954 66

Sub-lethal exposure to sarin (GB), a potent chemical warfare agent, produces long-term neurological deficits in both humans and rodents. However, rodents express much higher levels of carboxylesterase (CaE) than humans and require a much higher dose of GB in rodents to produce neurotoxicity. In mice, the combination of the carboxylesterase inhibitor 2-(o-cresyl)-4H-1:3:2-benzodioxaphosphorin-2-oxide (CBDP) with the organophosphorus (OP) nerve agent GB renders mice more sensitive to OP poisoning. After the reduction in CaE, GB inhibits acetylcholinesterase at doses similar to those in human toxicity. A dose-response curve for GB was determined in male C57BL/6 mice after 1.5mg/kg CBDP. A functional observational battery (FOB) for behavior was used to determine the dose needed to elicit seizure activity but maintain a mortality of less than 50%. Neuronal cell death was evaluated at 4, 7, 10 and 14 days post-GB exposure. Multiple brain areas were examined using cresyl violet: CA1 and the dentate gyrus of the hippocampus, amygdala and piriform cortex. GFAP staining was then measured as an index of cell death in the dentate gyrus of the hippocampus. The dentate gyrus and CA1 exhibited significant neuronal death indicated by both cresyl violet and GFAP staining. The treated animals also had a significant decrease in tissue and blood acetylcholinesterase, in addition to decreases in plasma CaE. CBDP renders mice more sensitive to the effects of GB exposure and mirrors a human symptomatic exposure dose.
 ...
PMID:A murine model for sarin exposure using the carboxylesterase inhibitor CBDP. 2051 Feb 97