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

A serum-free medium culture was developed in order to study the secretory behavior of neurons producing the melanin-concentrating hormone (MCH) precursor. The present results show that our culture conditions (supplemented RPMI 1640, poly-D-lysine substrate) are efficient in promoting attachment and growth of MCH neurons dissociated from rat fetal hypothalamus. These neurons acquire a differentiation stage in which neuropeptides of interest to us are expressed in a pattern similar to that observed on tissue sections: (1) coexpression of salmon MCH, growth-hormone-releasing factor (GRF37), alpha-melanocyte-stimulating hormone and acetylcholinesterase immunoreactivities, and (2) different intracellular distribution of salmon MCH and 1-37 sequence of GRF37 staining. Neurite growth was rapid and interneuronal connections were observed early. These observations suggest that our model of defined medium culture is suitable for functional investigations on MCH neurons.
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PMID:Expression of peptides derived from the melanin-concentrating hormone precursor in serum-free culture of rat fetal hypothalamic neurons: role of attachment factors. 180 58

Using an antiserum (AS) raised against rat cerebral acetylcholinesterase (AChE), we revealed a neuron population in lateral and dorsal areas of the posterior rat hypothalamus. These neurons were previously described using antibodies to human growth hormone-releasing factor(1-37) (GRF-37), alpha-melanotropin (alpha-MSH) and melanin-concentrating hormone (MCH). Different intracytoplasmic distributions of the immunodeposits were observed depending on the used serum. Ultrastructural investigations demonstrated that AChE-AS labeled rough endoplasmic reticulum and nuclear envelope in control rats. MCH-AS stained Golgi apparatus in control animals and secretory granules in colchicine-injected rats. GRF-37-AS always revealed secretory granules, and alpha-MSH-AS gave the same staining only after colchicine injection.
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PMID:Coexistence of acetylcholinesterase-, human growth hormone-releasing factor(1-37)-, alpha-melanotropin- and melanin-concentrating hormone-like immunoreactivities in neurons of the rat hypothalamus: a light and electron microscope study. 254 28

Groups of 21 male and 21 female Sprague-Dawley (SD) rats were fed diets containing pyriproxyfen at concentrations of 0, 80, 400, 2,000 and 10,000 ppm for 6 months. No death was found in any group. Alopecia in the neck and/or back, and soft feces were noticed in both sexes fed 10,000 ppm. A marked decrease in body weight gain was observed in both sexes fed 10,000 ppm throughout the treatment period, accompanying a decrease in food-consumption and an increase in water-intake during the initial stage of treatment. In terms of urinalysis, proteinuria, increases in K excretion, and, in number, yellowness or browish-yellowness in appearance, were observed in both sexes fed 10,000 ppm. In females fed 10,000 ppm, increases in bilirubin, Na excretion and specific gravity, and a decrease in ketone bodies, were observed. In hematology, decreases in erythrocyte count, hemoglobin concentration and hematocrit value, were observed in both sexes fed 10,000 ppm and in males fed 2,000 ppm. Also, an increase in MCH (in males), decreases in MCHC and platelet count (in females) were observed in 10,000 ppm group. Blood biochemistry revealed increases in total protein, albumin, alpha 2-globulin fraction, blood urea nitrogen, calcium (in both sexes fed 10,000 ppm), A/G ratio (in males fed 2,000 and 10,000 ppm), total cholesterol, phospholipid (in males fed 2,000 and 10,000 ppm, and in females fed 10,000 ppm), sodium (in females fed 2,000 and 10,000 ppm), gamma-glutamyl transpeptidase activity (in males fed 10,000 ppm) and alpha 1-globulin fraction (in females fed 10,000 ppm), and decreases in glucose, GOT (in both sexes fed 10,000 ppm), beta-globulin fraction (in males fed 2,000 and 10,000 ppm, and in females fed 10,000 ppm), GPT (in females fed 2,000 and 10,000 ppm), triglyceride, potassium (in males fed 10,000 ppm), and cholinesterase activity (in female fed 10,000 ppm). In organ weight, increases in liver (in males fed 2,000 ppm and 10,000 ppm, and in females fed 10,000 ppm), kidney (in both sexes fed 10,000 ppm) and thyroid (in females fed 10,000 ppm) and a decrease in pituitary (in females fed 2,000 and 10,000 ppm) were observed. Gross pathology revealed a higher incidence of blackish-brown coloration of the liver, and a lower incidence of accentuated lobular pattern of the liver (in males fed 10,000 ppm). An enlargement of the liver was seen in a few of both sexes fed 10,000 ppm. Histopathological examination showed that the sole effect attributable to treatment of this compound was on slight hypertrophy in the liver of both sexes fed 10,000 ppm, with a higher incidence.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[A six-month chronic dietary toxicity study of pyriproxyfen in rats]. 273 65

52-week oral repeated-dose S-1 toxicity studies were conducted. Male and female dogs were orally treated with 0, 0.1, 0.5 or 2.5 mg/kg/day for 52 weeks and permitted to recover for 13 weeks. Furthermore, to estimate the no-toxic dose, male and female dogs were given S-1 orally for 52 weeks at doses of 0, 0.004 and 0.02 mg/kg/day. The 2.5 mg/kg/day regimen produced one dead or moribund dog of each sex; black-brown patch (melanin deposition) and inflammatory changes in the eyes and skin; decreased in body weight gains; increases in MCV, MCH, monocyte ratio, and serum protein and uric acid; decreases in lymphocyte ratio and erythrocyte count, hematocrit, hemoglobin, albumin, A/G ratio, cholesterol (esterified, total and free), phospholipids, triglycerides, cholinesterase activity and creatinine; increases in relative liver and adrenal weights. Histopathological examinations revealed melanin deposits in superficial lymph nodes, increases in macrophage and plasma cell accumulation, and corneal atrophy accompanied by melanin deposits and capillary proliferation. A slight black-brown patch (melanin deposition) in the conjunctiva and skin was observed in the 0.1 and 0.5 mg/kg/day groups. No drug-related changes were observed in groups that received 0.02 and 0.004 mg/kg/day. All changes observed during the treatment period disappeared during recovery except for melanin deposits in the conjunctiva and superficial lymph nodes, corneal opacity, and a few hematological and blood chemistry parameters. In conclusion, the no-toxic dose in these 52-week studies was estimated to be 0.02 mg/kg/day.
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PMID:[A 52-week oral toxicity study of a new antineoplastic agent S-1 in dogs]. 902 62

Chronic toxicity and carcinogenicity of polyoxyethylene(10)nonylphenyl ether (NP-10) to Fischer 344 rats were investigated using 70 females per group in 4 study groups, or 280 rats in total. Diets containing NP-10 at 0, 1000, 3000 and 9000 ppm were prepared and orally administered to the animals repeatedly for 52 weeks for a chronic toxicity study and for 104 weeks for a carcinogenicity study. Observations of general condition, body weight analysis, food consumption analysis, hematologic examination, blood chemistry examination (only at Week 52 of administration), urinalysis (only at Week 52), ophthalmologic examination (immediately prior to administration and at Week 52), organ weight analysis and pathological examination were performed. The results are summarized as follows. The mean intake of the test substance was 60.5, 182 and 559 mg/kg/day in the chronic toxicity study for 52 weeks and 55.2, 166 and 520 mg/kg/day in the carcinogenicity study for 104 weeks in the 1000, 3000 and 9000 ppm groups, respectively. Mortality decreased approximately in a dose-related manner, with 28% in the control group, 26% in the 1000 ppm group, and 14% each in the 3000 and 9000 ppm groups. In general condition, there were no signs attributed to the treatment with NP-10. Body weight gain was suppressed in the 9000 ppm group throughout the administration period and in the 3000 ppm group during Weeks 21-88. Food consumption decreased in the 9000 and 3000 ppm groups. Food efficiency was lower in the 9000 and 3000 ppm groups. As a result of the hematologic examination, hematocrit value, hemoglobin value, red blood cell count, platelet count and MCV were lower and MCH and MCHC higher in the 9000 ppm group at Week 52 of administration. At Week 104, the neutrophil ratio was higher and lymphocyte ratio lower in the 3000 and 9000 ppm groups, and furthermore, hematocrit value, hemoglobin value, MCV and MCH were slightly lower in the 9000 ppm group. In the blood coagulability tests, prothrombin time was slightly shortened in the 9000 ppm group at Week 52. As a result of the blood chemistry examination, total protein and albumin values were higher and total bilirubin, uric acid and trygliceride value lower in the 3000 ppm and higher dose groups. Furthermore, the free cholesterol value was higher and the values of potassium, cholesterol ester ratio, GOT, GPT, ALP and cholinesterase were lower in the 9000 ppm group. As a result of the urinalysis, the specific gravity of urine was higher and urine pH acidic in some animals. As a result of the ophthalmologic examination, no abnormal animals were found in the 9000 ppm group. As a result of the organ weight analysis, absolute and relative weights of the liver and adrenals were higher in the 3000 and/or 9000 ppm groups as changes which were considered attributable to the test substance and, in addition, organs with a lower absolute weight and higher relative weight with the suppressed body weight gain were observed in the 9000 ppm group. The histopathological examination revealed no marked findings in necropsy observation or histology in the treated groups in the animals killed at Weeks 52, 104 as well as those killed moribund and dead animals. In the histological findings, bile duct hyperplasia of liver in the animals killed at Week 52, proliferative duct of pancreas in the animals killed at Week 104, pigment of deposit in pituitary and angiectasis of adrenals in the animals killed at moribund and dead animals were observed in a slightly larger number in the treated groups, but none of these changes were different in degree from the control and were not considered to be specific lesions. As a result of the overall study of the neoplastic lesions of all animals killed on schedule and of moribund and dead animals, no tumors were found in the treated groups which had increased in occurrence. Based on the above findings, it was determined that the no-adverse-effect level in the chronic toxicity study was 1000 ppm (
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PMID:Oral chronic toxicity and carcinogenicity test of polyoxyethylene(10)nonylphenyl ether (NP-10) in female F344 rats. 1066 63

The lateral hypothalamic area (LHA) contains a large population of neurons that express the enzyme acetylcholinesterase (AChE), but are not themselves cholinergic. Some of these neurons have been shown to contain melanin-concentrating hormone (MCH), a neuropeptide implicated in regulating feeding, but the identities of the remaining neurons are unknown. We now report that nearly all AChE-immunoreactive neurons in the LHA express immunoreactivity for either MCH or for orexin, a peptide implicated in regulating wakefulness. Furthermore, most orexin neurons and MCH neurons appear to contain AChE. AChE immunoreactivity appears to be a key feature of nearly all of the diffusely-projecting cortical systems.
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PMID:Lateral hypothalamic acetylcholinesterase-immunoreactive neurons co-express either orexin or melanin concentrating hormone. 1548 7

Bronchial hyperresponsiveness (BHR) is a common feature in the majority of asthmatic subjects and methacholine is the most frequently used agent for the test. The influence of 3 or 5 min time intervals between doses steps in a double methacholine challenge test (MCH-3' or MCH-5') was investigated. Using the MCH-3' challenge, 52 intermittent asthmatics were classified as having moderate (BHR-M; 18 subjects), mild (BHR-m; 19 subjects), or bordeline (BHR-B; 15 subjects) BHR. The cumulative dose and the PD20FEV(1) were higher for MCH-5' compared with MCH-3' in BHR-m (p < 0.05) and BHR-B (p < 0.05) but not in the BHR-M group. Also the dose response slopes, FEV(1)% decline/cumulative methacholine dose, calculated for the two challenge tests were statistically different only in BHR-m (p < 0.05) and BHR-B (p < 0.01). At MCH-5', there were 16 subjects with BHR-M, 18 with BHR-m, 12 with BHR-B and 6 subjects with normal reactivity. Results may suggest that in the group of BHR-m and BHR-B subjects, at MCH-5' compared with MCH-3', the cumulative effect of the administered drug, quickly metabolized by cholinesterase, is not complete, thus leading to an incorrect estimation of bronchial hyperresponsiveness degree. It is hoped that time interval between doses be standardized to ensure maximum comparability within and between subjects in challenge tests.
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PMID:Time intervals (3' or 5') between dose steps can influence methacholine challenge test. 1579 63

The organization of the adult human medial preoptic nucleus was studied by using chemoarchitectonic markers for acetylcholinesterase, nonphosphorylated neurofilament protein (SMI-32), calbindin-D28k, neuropeptide Y (NPY), melanin-concentrating hormone (MCH), cocaine- and amphetamine-regulated transcript (CART), and 3-fucosyl-N-acetyl-lactosamine (CD15) to establish human homologs to the subnuclei making up MPO in the rat, where their connections and functional significance are better understood. The human MPO comprises three subnuclei, the medial MPO, the lateral MPO, and the dorsomedially positioned uncinate subnucleus. As in the rat, the human medial MPO is magnocellular and contains numerous NPY- and CART-immunoreactive fibers and terminals as well as calbindin-positive neurons. The human lateral MPO, like its homolog in the rat, distinctively features numerous MCH-positive fibers and terminals as well as SMI-32-immunoreactive fibers. The uncinate subnucleus is wedged between the lateral surface of the paraventricular nucleus and the medial MPO and is characterized by variable NPY- and CART-immunoreactive fibers and terminals, also seen in the rat central MPO, suggesting that the subnuclei are homologues. The intermediate nucleus was distinguished by CD15-positive neuronal staining, whereas the majority of its neurons also contained acetylcholinesterase. The human intermediate nucleus is positioned on the lateral surface of MPO and by its chemo- and cytoarchitecture constitutes a distinct nucleus of the preoptic area characterized by close structural association with the MPO complex. These findings demonstrate that the human MPO is organized similarly to the rat MPO, in chemo- and cytoarchitectonically distinct subnuclei, which implies differences in their functional specialization, as seen in the rat.
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PMID:Organization of the human medial preoptic nucleus. 1750 90

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