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

---

Query: EC:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has long been suggested that acetylcholinesterase is capable of functioning in a non-cholinergic manner. However, very little is known about the molecular structures which mediate the interaction between this protein and the cellular membrane. Previously it was demonstrated that acetylcholinesterase interacted in a carbohydrate-specific manner with peritoneal macrophages and induced the 'respiratory burst' [1]. This study aimed to establish whether a carbohydrate-binding site exists on the acetylcholinesterase molecule itself, or alternatively, whether the macrophage carbohydrate-binding receptor is involved. No carbohydrate binding properties intrinsic to acetylcholinesterase were detected using affinity chromatography with immobilised monosaccharides, erythrocyte agglutination and gel-diffusion techniques. The interaction between acetylcholinesterase and several monosaccharide columns observed in this study appeared to be due to ionic interactions. Moreover, it was shown that a specific inhibitor of the enzymatic activity of AChE, BW284C51, could inhibit the peritoneal cell response not only to acetylcholinesterase, but also to several other stimuli, thus exhibiting a non-specific effect on macrophages. However, the inhibitory effects of specific ligands of the macrophage mannose-fucose receptor and the inability of non-glycosylated acetylcholinesterase to interact with macrophages suggested that the effect of acetylcholinesterase on peritoneal cells is most probably mediated by the macrophage mannose-fucose receptor. The role of the mannose-fucose receptor in triggering the respiratory burst response was supported by the fact that several ligands of these receptors were capable of inducing the functional response of macrophages.
...
PMID:Acetylcholinesterase-induced respiratory burst in macrophages: evidence for the involvement of the macrophage mannose-fucose receptor. 860 27

In earlier studies we have shown that a final concentration of 0.69% glycerol in blood mixed with an experimental additive solution, EAS 25, improves the in vitro quality and in vivo survival of red blood cells (RBCs). The objective of this study was to determine if the better preservation of RBCs in EAS 25 is correlated with the improved maintenance of membrane lipids and proteins and decreased vesiculation. Split units of RBCs were stored in Adsol or EAS 25 (mmol/L: adenine 2/2, dextrose 122/110, mannitol 42/55, glycerol 0/150, NaCl 154/50). After 12 weeks storage, RBC and microvesicle membranes were analyzed for cholesterol, phospholipid, diphenyl hexatriene fluorescence anisotropy, and acetylcholinesterase (AchE) activity. Bands 3 and 4.1 were identified in the microvesicle membranes by immunoblotting. The RBC membrane cholesterol, phospholipids, and AchE remained higher in EAS 25 than in Adsol (P < .001). Vesicle membrane lipids and AchE in EAS 25 were significantly less than in Adsol (P < .001). The fluidity of stored cells in both the solutions was greater than the prestorage samples. Immunoblotting analyses showed that bands 3 and 4.1 were greatly reduced in the microvesicle membranes shed by the RBCs stored in EAS 25 compared with those formed in Adsol.
...
PMID:Improved red blood cell preservation correlates with decreased loss of bands 3, 4.1, acetylcholinestrase, and lipids in microvesicles. 860 55

Primary sclerosing cholangitis, a chronic cholestatic liver disease, frequently leads to an impairment of liver function. In nine men and two women, aged 23 to 57 years, we prospectively studied for three to six years the effect of treatment with ursodeoxycholic acid (UDCA) on liver function. 10 mg UDCA/kg bw significantly reduced serum activities of AP, gamma GT, AST and ALT for several years. After three years of treatment, however, serum concentration of bilirubin was higher than before therapy in eight out of eleven patients (1.8 +/- 0.8 versus 0.9 +/- 0.1 mg/dl; p = 0.01). Likewise, serum concentration of bilirubin was higher in eight out of nine patients after four years of treatment (1.3 +/- 0.3 versus 0.9 +/- 0.1 mg/dl; p = 0.03). In most cases, however, the increase was discrete. Parameters of synthetic liver function (coagulation, serum protein concentration, serum activity of cholinesterase) remained constant in the observation time. Quantitative liver function tests (galactose elimination capacity and indocyanine green half-life) also showed little variation in the observation time. We conclude that UDCA treatment significantly improves serum activities of liver enzymes for several years. Nevertheless, serum bilirubin concentration, believed to be of prognostic value in patients with PSC, seems to rise slowly over time. Serial determinations of galactose elimination capacity and indocyanine green halflife are not superior to conventional liver function tests in the timing of liver transplantation in the individual patient.
...
PMID:[Primary sclerosing cholangitis: conventional and quantitative liver function tests during long-term therapy with ursodeoxycholic acid]. 865 87

Alpha 1-Antitrypsin deficiency predisposes to pulmonary emphysema, liver cirrhosis and hepatocellular carcinoma. Anecdotal evidence and a large autopsy study suggest that severe lung and liver disease rarely coexist in the same subject, but this has not been studied in patients. Therefore we investigated 27 patients with severe alpha 1-deficiency (Pi ZZ) and pulmonary emphysema for signs of liver disease and impaired hepatic function. A subgroup of 7 patients underwent quantitative liver function tests. On physical examination or ultrasonography, cirrhosis or tumor was not suspected in any patient. Conventional liver function tests were completely normal in 17 patients. Elevated serum activities of gamma-glutamyltranspeptidase and/or aminotransferases were seen in 10 patients. In some, the elevation was only marginal and in none more than twice normal. The serum bilirubin concentration and activity of alkaline phosphatase were increased in 1 patient. Serum protein, albumin, fibrinogen, antithrombin III, alpha 1-fetoprotein concentrations, serum activities of cholinesterase and glutamate dehydrogenase, activated partial thromboplastin time and prothrombin time were normal in all patients. The indocyanine green half-life was abnormal only in 1 of 6 patients, suggesting that hepatic blood flow was not impaired in the study group. However, the lidocaine half-life and galactose elimination capacity, parameters of hepatic metabolization, were impaired in 4 and 6 of 7 patients, respectively. We conclude that liver disease or impaired liver function is not a clinically relevant problem in most patients with pulmonary emphysema due to alpha 1-antitrypsin deficiency. But results of quantitative liver function tests, although performed in only a small group of patients, suggest that hepatic metabolization might be impaired even in those patients who present with pulmonary disease.
...
PMID:Liver function in patients with pulmonary emphysema due to severe alpha-1-antitrypsin deficiency (Pi ZZ). 873 89

The effects of scopolamine, a muscarinic cholinergic receptor antagonist and physostigmine, a cholinesterase inhibitor, on the regional cerebral blood flow (rCBF) response to vibrotactile stimulation of the forepaw were studied in the brain of unanesthetized monkeys using 15O-labeled water and high resolution positron emission tomography. Before scopolamine administration, vibrotactile stimulation produced a significant increase in the rCBF response in the contralateral somatosensory cortex of the monkey brain. Intravenous administration of scopolamine at doses ranging from 1 to 500 microg/kg resulted in a dose-dependent reduction of the rCBF response. The rCBF response abolished by scopolamine (50 microg/kg) was recovered by administration of physostigmine (10 microg/kg). On the other hand, the regional cerebral metabolic rate of glucose (rCMRglc) response, measured with [18F]-2-fluoro-2-deoxy-D-glucose, to the same stimulation was unchanged by administration of either scopolamine and/or physostigmine. These results suggested that cholinergic mechanisms might be involved in regulation of the coupling between neuronal activity and rCBF response, not between the activity and rCMRglc response.
...
PMID:Regulation of cerebral blood flow response to somatosensory stimulation through the cholinergic system: a positron emission tomography study in unanesthetized monkeys. 907 Jun 22

Cholinesterases are serine hydrolases that can potentially be used as pretreatment drugs for organophosphate toxicity, as drugs to alleviate succinylcholine-induced apnea, and as detoxification agents for environmental toxins such as heroin and cocaine. The successful application of serum-derived cholinesterases as bioscavengers stems from their relatively long residence time in the circulation. To better understand the relationship between carbohydrate structure and the stability of cholinesterases in circulation, we determined the monosaccharide composition, the distribution of various oligosaccharides, and the structure of the major asparagine-linked oligosaccharides units present in fetal bovine serum acetylcholinesterase and equine serum butyrylcholinesterase. Our findings indicate that 70-80% of the oligosaccharides in both enzymes are negatively charged. This finding together with the molar ratio of galactose to sialic acid clearly suggests that the beta-galactose residues are only partially capped with sialic acid, yet they displayed a long duration in circulation. The structures of the two major oligosaccharides from fetal bovine serum acetylcholinesterase and one major oligosaccharide from equine serum butyrylcholinesterase were determined. The three carbohydrate structures were of the biantennary complex type, but only the ones from fetal bovine serum acetylcholinesterase were fucosylated on the innermost N-acetylglucosamine residue of the core. Pharmacokinetic studies with native, desialylated, and deglycosylated forms of both enzymes indicate that the microheterogeneity in carbohydrate structure may be responsible, in part, for the multiphasic clearance of cholinesterases from the circulation of mice.
...
PMID:Structure of glycan moieties responsible for the extended circulatory life time of fetal bovine serum acetylcholinesterase and equine serum butyrylcholinesterase. 920 Jun 97

Effect of TAK-147, a novel acetylcholinesterase (AChE) inhibitor, on cerebral energy metabolism was investigated using an in vivo 31P-magnetic resonance spectroscopy (31P-MRS) technique and the autoradiographic 2-deoxy-[14C]-D-glucose method in aged Fischer 344 rats. We revealed that high-energy phosphate metabolites, phosphocreatine (PCr) and ATP, in the brain decreased gradually with aging and that significant decrement of cerebral PCr and ATP was observed from 13- and 8.5-month-old in comparison with those of 2.5-month-old rats, respectively. Daily oral administration of TAK-147 (1 mg/kg) for 40 days increased PCr and ATP levels in aged rats (29-month-old). To determine the site at which TAK-147 acts to increase high-energy phosphate metabolism, we investigated the rate of local cerebral glucose utilization (LCGU) in various brain regions. The rate of LCGU decreased in almost all brain regions in aged rats (28 months of age), and the decrease was significant in 29 out of the 35 regions. When TAK-147 was administered orally to the aged rats, the levels were dose dependently increased, especially in the auditory cortex. These results indicate that TAK-147 increases cerebral energy metabolism in aged rats.
...
PMID:Effect of TAK-147, a novel AChE inhibitor, on cerebral energy metabolism. 936 95

Parallel increments of gastric acid and pepsinogen secretion generally occur after the application of cholinergic stimuli. However, it still remains to be established whether the changes in acid output associated with cholinergic stimulation play a role in regulation of the concomitant peptic secretory activity. In the present study, an anesthetized rat model was used for the evaluation of pepsinogen secretion in order to pursue a dual purpose: 1) to assess the relative functional relevance of direct and acid-dependent control exerted by cholinergic pathways on pepsinogen output; 2) to characterize the mechanisms through which changes in acidity within the stomach lumen may affect the peptic secretory activity of gastric mucosa. Bethanechol, 2-deoxy-D-glucose or electrical vagal stimulation caused parallel and atropine-sensitive increments of peptic and acid secretions. Omeprazole, a selective inhibitor of gastric H+:K+-adenosintriphosphatase, blocked the increase in acid but not pepsinogen secretion induced by bethanechol. However, 2-deoxy-D-glucose or electrical vagal stimulation failed to increase either pepsinogen or acid secretion in omeprazole-pretreated rats. When tested in animals pretreated with both omeprazole and physostigmine (a drug able to prevent the enzymatic breakdown of vagally released ACh through the blockade of acetylcholinesterase), 2-deoxy-D-glucose or electrical vagal stimulation significantly increased pepsinogen secretion without affecting acid secretion. In omeprazole-pretreated rats, perfusion of the gastric lumen with acid solutions caused a pH-dependent and atropine-sensitive increase in peptic output only when applied in combination with electrical vagal stimulation. Functional ablation of capsaicin-sensitive sensory neurons did not modify the gastric secretory responses induced by bethanechol or electrical vagal stimulation. However, after topical application of lidocaine to the gastric mucosal surface, bethanechol stimulated both peptic and acid outputs, whereas electrical vagal stimulation only evoked acid secretion without affecting basal peptic output. The present results indicate that the activation of muscarinic receptors by vagally released ACh is not sufficient by itself to stimulate pepsinogen secretion and that a facilitatory action mediated by acid secretion is necessary to allow an increment of peptic output in response to vagal cholinergic stimuli. It is suggested that such facilitatory input is driven to chief cells by local intramural reflexes that involve capsaicin-insensitive intrinsic nerves.
...
PMID:Positive modulation of pepsinogen secretion by gastric acidity after vagal cholinergic stimulation. 939 75

To understand the role of glycosylation in the circulation of cholinesterases, we compared the mean residence time of five tissue-derived and two recombinant cholinesterases (injected intravenously in mice) with their oligosaccharide profiles. Monosaccharide composition analysis revealed differences in the total carbohydrate, galactose, and sialic acid contents. The molar ratio of sialic acid to galactose residues on tetrameric human serum butyrylcholinesterase, recombinant human butyrylcholinesterase, and recombinant mouse acetylcholinesterase was found to be approximately 1.0. For Torpedo californica acetylcholinesterase, monomeric and tetrameric fetal bovine serum acetylcholinesterase, and equine serum butyrylcholinesterase, this ratio was approximately 0.5. However, the circulatory stability of cholinesterases could not be correlated with the sialic acid-to-galactose ratio. Fractionation of the total pool of oligosaccharides obtained after neuraminidase digestion revealed one major oligosaccharide for human serum butyrylcholinesterase and three or four major oligosaccharides in other cholinesterases. The glycans of tetrameric forms of plasma cholinesterases (human serum butyrylcholinesterase, fetal bovine serum acetylcholinesterase, and equine serum butyrylcholinesterase) clearly demonstrated a reduced heterogeneity and higher maturity compared with glycans of monomeric fetal bovine serum acetylcholinesterase, dimeric tissue-derived T. californica acetylcholinesterase, and recombinant cholinesterases. T. californica acetylcholinesterase, recombinant cholinesterases, and monomeric fetal bovine serum acetylcholinesterase showed a distinctive shorter mean residence time (44-304 min) compared with tetrameric forms of plasma cholinesterases (1902-3206 min). Differences in the pharmacokinetic parameters of cholinesterases seem to be due to the combined effect of the molecular weight and charge- and size-based heterogeneity in glycans.
...
PMID:Role of oligosaccharides in the pharmacokinetics of tissue-derived and genetically engineered cholinesterases. 944 38

The effects of somatosensory stimulation on the regional cerebral blood flow (rCBF) response were studied in unanesthetized monkeys under modulations of the glutamatergic and cholinergic systems using [15O]H2O and positron emission tomography (PET). Under a saline condition, vibrotactile stimulation elicited a significant increase in the rCBF response in the contralateral somatosensory cortex. The systemic administration of scopolamine, a muscarinic cholinergic receptor antagonist, resulted in the dose-dependent reduction of the rCBF response to the stimulation. The rCBF response abolished by scopolamine was recovered by the administration of physostigmine, a cholinesterase inhibitor in a dose-dependent manner. In addition, D-cycloserine, a partial agonist at the glycine site coupled to N-methyl-D-aspartate (NMDA) receptors, also restored the scopolamine-abolished rCBF response. The regional cerebral metabolic rate of glucose (rCMRglc) response, measured with [18F]-2-fluoro-2-deoxy-D-glucose, was not affected by the administration of scopolamine, physostigmine and/or D-cycloserine. The systemic administration of (+)-3-amino-1-hydroxy-2-pyrrolidone (HA-966), an antagonist of the glycine modulatory site on the NMDA receptors, induced the dose-dependent suppression of the rCBF response to the stimulation. The rCBF response abolished by HA-966 was restored by D-cycloserine, but not by physostigmine. The rCMRglc response was partially but significantly reduced by the administration of HA-966, and its reduction was restored by D-cycloserine, but not by physostigmine. These findings provided pharmacological evidence for an interaction between cholinergic and glutamatergic neuronal systems, the latter of which mediates the former by downstream regulation, in the functional rCBF response to somatosensory stimulation.
...
PMID:Interactions of cholinergic and glutamatergic neuronal systems in the functional activation of cerebral blood flow response: a PET study in unanesthetized monkeys. 968 57


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---