Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the present work was to evaluate the effect on the growth hormone (GH) secretion of eptastigmine, a new long-acting cholinesterase inhibitor, in unanesthetized beagle dogs. In a first study, 5 young dogs were given single doses (0.5, 1.0, and 2.0 mg/kg, i.m.) of the drug or saline in a randomized cross-over manner. Blood samples were collected immediately before and, at regular intervals, until 150 min after drug injection. GH plasma concentrations were determined by radioimmunoassay. Plasma cholinesterase activity was measured with a potentiometric method. There was a significant logistic relationship (r = 0.601, P < 0.01) between the administered dose of eptastigmine and the log-transformed areas under the GH plasma concentration-time curve (AUC) with a calculated ED50 for eptastigmine of 0.63 +/- 0.36 mg/kg. There was also a significant linear relationship (r = 0.630, P < 0.01) between log-transformed AUC of GH levels and AUC of plasma cholinesterase activity. In a second study we evaluate the ability of eptastigmine (2.0 mg/kg, i.m.) to potentiate the GH-releasing effect of the GH-releasing hormone (GHRH, 2.0 micrograms/kg, i.v.) in young and old dogs. Eptastigmine was administered 45 min before GHRH and blood collected every 15 min until 90 min after GHRH injection. In young dogs, maximum GH plasma levels (Cmax) were 6.1 +/- 1.0 ng/ml after GHRH compared to 22.5 +/- 2.3 ng/ml after GHRH preceded by eptastigmine (P < 0.01). In old animals, Cmax were 4.6 +/- 1.4 ng/ml after GHRH vs 13.2 +/- 7.4 ng/ml after combined administration of GHRH and eptastigmine (P < 0.05). These data indicate that eptastigmine is very effective in augmenting basal and stimulated GH secretion in old dog. The good activity also shown in old animals suggests a potential use of this drug to reverse the age-dependent decline in GH secretion responsible for many involutional changes of aging.
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PMID:Eptastigmine augments basal and GHRH-stimulated growth hormone release in young and old dogs. 833 17

The aim of this study was to investigate the regulation of various proteins of the GHIGF axis during progression of liver failure and to search for potential prognostic markers of functional hepatic reserve. Serum levels of growth hormone (GH) and high affinity growth hormone binding protein (GHBP), insulin-like growth factor I (IGF-I) and IGF binding proteins (IGFBP) -1, -2 and -3 were determined in patients with liver cirrhosis. A continuous decline in the concentrations of IGF-I, IGFBP-3 and serum GH-binding activity (GHBP) was observed during progression of cirrhosis and the data correlated significantly with choline esterase, total serum protein and the Child score. In addition, GHBP showed a significant correlation with the enzymatic activity of glutamate dehydrogenase or transaminases and seems so to be influenced by the degree of liver cell damage. In contrast, IGFBP-1 and IGFBP-2 levels were significantly elevated in preterminal disease suggesting an upregulatory mechanism is still effective in this situation. Only when liver function had markedly deteriorated, the serum levels of these two parameters decreased again, possibly due to an impaired synthesis. The excellent correlation between the serum levels of IGF-I (r = -0.64, p < 0.001) or IGFBP-3 (r = -0.67, p < 0.001) and the Child score index suggests that they reflect the hepatic functions just as conventional indicators. For an appropriate interpretation of the liver function the measurement of the growth related peptides can be a valuable tool to estimate pathological alteration in the functional hepatic reserve or in the glucose homeostasis.
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PMID:Regulation of growth hormone (GH), insulin-like growth factor (IGF)I, IGF binding proteins -1, -2, -3 and GH binding protein during progression of liver cirrhosis. 853 56

In human, arginine (ARG) induces growth hormone (GH) release, probably via a decrease in somatostatinergic tone. To assess the mechanism by which ARG mediates GH release in pigs, the effects on plasma GH release of ARG (1 g/kg body weight, infused between times -15 and -5 min), growth hormone-releasing hormone (GHRH, 2 micrograms/kg, at time 0 min) and neostigmine, a cholinesterase inhibitor (NEO, 50 micrograms/kg, at time 4 min), administered intravenously singly or in paired combinations were investigated in piglets between times -30 and 100 min. ARG and GHRH had additive effects on GH release. No potentialization was observed between the two treatments. GH response was higher following the combination of NEO and GHRH treatments than after NEO or GHRH given alone. NEO had no further effect on ARG-induced GH secretion. Therefore, our results suggest that the mechanism by which ARG stimulates GH secretion in pig is the same as in human.
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PMID:Effects of arginine, growth hormone-releasing hormone (GHRH) and neostigmine administered singly or in paired combinations on growth hormone (GH) release in pigs. 943 57

There are data indicating that cholinergic activity is precociously impaired in Down's syndrome (DS). On the other hand, acetylcholine as well as arginine (ARG) play a major stimulatory role in the neural control of growth hormone (GH) secretion in humans, likely acting via the inhibition of hypothalamic somatostatin release. The aim of the present study was to verify the effects of pyridostigmine (PD, 120 mg p.o.), a cholinesterase inhibitor, and ARG (0.5 g/kg i.v.) on the growth hormone-releasing hormone (GHRH) (1 microgram/kg i.v.)-induced GH rise in 15 adult patients with DS (M/F: 8/7; age 26.5 +/- 2.2 years; body mass index, BMI: 25.7 +/- 1.0 kg/m2) in which the potentiating effect of PD on GH secretion has been reported to be reduced. The results in DS were compared to those in 15 normal subjects (NS) (M/F: 8/7; age: 30.0 +/- 1.3 years; BMI: 21.4 +/- 0.4 kg/m2). Basal GH and insulin growth factor I (IGF-1) levels in DS (1.8 +/- 0.7 and 206.5 +/- 21.0 micrograms/l) were similar to those in NS (1.4 +/- 0.3 and 179.4 +/- 11.0 micrograms/l). The GH response to GHRH alone in DS (526.5 +/- 120.1 micrograms/l/h) was lower (p < 0.05) than that recorded in NS (895.4 +/- 153.7 micrograms/l/h). The GHRH-induced GH rise was potentiated by PD both in DS (1,138 +/- 184.2 micrograms/l/h; p < 0.02 vs. GHRH alone) and in NS (2,213.8 +/- 212.8 micrograms/l/h; p < 0.005 vs. GHRH alone); however, as the percent potentiating effect of PD was similar in both groups (215 and 247%, respectively) the GH response to GHRH + PD in DS was lower (p < 0.005) than that in NS. The GHRH-induced GH rise was also potentiated by ARG in both DS (2,243 +/- 362.4 micrograms/h; p < 0.001 vs. GHRH alone) and NS (2,764.3 +/- 325.7 micrograms/l/h; p < 0.005 vs. GHRH alone). As the percent potentiating effect of ARG in DS was more marked than in NS (425 vs. 308%, respectively), the GH response to GHRH + ARG became similar in both groups. No sex-related difference was found in the GH response to various stimuli both in DS and NS. In conclusion, these data demonstrate that the potentiating effect of PD but not that of ARG is impaired in adults with DS in whom a reduced somatotrope responsiveness to GHRH is present. These findings indicate that in DS the pituitary GH releasable pool is fully preserved while an impairment of the tuberoinfundibular cholinergic pathways could lead to somatostatinergic hyperactivity and low somatotrope responsiveness to GHRH.
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PMID:Further evidence of cholinergic impairment of the neuroendocrine control of the GH secretion in Down's syndrome. 952 98

A chronic treatment with a cholinesterase inhibitor, donepezil (0.085 mg/kg/h for 30 days) increases significantly the number and amplitude of growth hormone (GH) pulses in 3- and 24-month-old rats without modifying nadir GH values. This treatment does not reduce age-related alterations in sleep/wake cycle but it increases immobility-related high-voltage spindles (HVS) in old animals. These data suggest that cholinergic mechanisms involved in age-related alterations in GH and sleep regulation are different.
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PMID:Donepezil restores GH secretion in old rats without affecting the sleep/wake cycle. 1619 9

Acylated (octanoylated) ghrelin stimulates food intake and growth hormone secretion and is deacylated into desacyl ghrelin by butyrylcholinesterase. Acylated and desacyl ghrelin both promote adipogenesis. Ghrelin concentrations decrease with hyperglycemia and hyperinsulinism. We hypothesized that 1) acylated ghrelin increases during pregnancy, contributing positively to energy balance, but is lower in women with gestational diabetes and 2) butyrylcholinesterase activity is inversely correlated with acylated ghrelin concentrations. In a first group of subjects, using two-site sandwich ghrelin assays that specifically detect full-length forms, we investigated women with and without gestational diabetes (n = 14/group) during pregnancy and after delivery. We examined whether changes in ghrelin during a test meal were correlated with changes in pituitary growth hormone [assessed through calculation of the area under the curve (AUC) during the test meal]. In postpartum subjects, the percent of total ghrelin that is acylated was four to five times higher than previously observed using single antibody assays. During pregnancy, acylated ghrelin concentrations (mean +/- SE) were lower compared with the postpartum period throughout the meal (AUC 1.2 +/- 0.2 vs. 10.2 +/- 1.9 ng.ml(-1).90 min(-1), P < 0.001). In the postpartum, acylated ghrelin and growth hormone were positively correlated (r = 0.50, P = 0.007). Desacyl (but not acylated) ghrelin was increased in subjects with gestational diabetes during and after pregnancy (AUC 15.4 +/- 1.9 vs. 8.6 +/- 1.2 ng.ml(-1).90 min(-1), P = 0.005). In a second group of subjects (n = 13), acylated ghrelin was similarly suppressed during pregnancy. Circulating octanoate concentrations (3.1 +/- 0.5 vs. 4.5 +/- 0.6 microg/ml, P = 0.029) and cholinesterase activity (705 +/- 33 vs. 1,013 +/- 56 U/ml, P < 0.001) were lower during pregnancy compared with the postpartum period. In conclusion, acylated ghrelin markedly decreases during pregnancy, likely because of a decrease in the acylation process. Desacyl ghrelin increases in gestational diabetes, possibly reflecting resistance to the inhibitory effect of insulin on ghrelin secretion.
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PMID:Acylated ghrelin concentrations are markedly decreased during pregnancy in mothers with and without gestational diabetes: relationship with cholinesterase. 1924 Feb 52

Alzheimer's disease (AD) has been traditionally conceptualized as a clinicopathological entity, its definite diagnosis requiring the presence of characteristic pathology together with a dementia clinical picture. The fact that certain AD biomarkers show an acceptable sensitivity and specificity to detect AD pathology has shifted the diagnostic paradigm towards a clinicobiological approach. Neuropathological analysis of AD-affected brains reveals extensive atrophy due to neuronal loss, and accumulation of neurofibrillary tangles and neuritic plaques, surrounded by a tract of neuroinflammation and loss of neurons. Recently, emerging evidence supports the concept that AD is also a disorder of metabolic degeneration. Taken together, the neurochemical changes in the brain from patients with AD indicate multiple disturbances and it seems likely that the changes are secondary to more fundamental changes into the brain. There is a physiological decline of the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis with ageing and the possibility that the GH/ IGF-I axis is involved in cognitive deficits has been recognized for several years. The IGF-I is a potent neurotrophic as well neuroprotective factor found in the brain with a wide range of actions in both central and peripheral nervous system. IGF-I is a critical promoter of brain development and neuronal survival and plays a role in neuronal rescue during degenerative diseases. The investigations of GH releasing stimulation tests especially to GHRH in AD are equivocal and in some cases contradictory. When a cholinesterase inhibitor as rivastigmine, a drug for AD, is acutely administered the area under the curve of the GH response to GHRH doubled, showing that rivastigmine is a powerful drug to enhance GH release. Starting with a more accurate diagnosis not of the clinical syndrome, but of underlying molecular defects, that may eventually lead to a personalized, more effective treatment. Hence, the development of novel therapeutic approaches is urgently needed.
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PMID:Possible usefulness of growth hormone/insulin-like growth factor-I axis in Alzheimer's disease treatment. 2252 98

The effects of growth hormone (GH) deficiency on the developmental changes in the abundance and activity of cholinesterase enzymes were studied in the developing spinal cord (SC) of postnatal rats by measuring the specific activity of acetylcholinesterase (AChE), a marker for cholinergic neurons and their synaptic compartments, and butyrylcholinesterase (BuChE), a marker for glial cells and neurovascular cells. Specific activities of these two enzymes were measured in SC tissue of 21- and 90 day-old (P21, weaning age; P90, young adulthood) GH deficient spontaneous dwarf (SpDwf) mutant rats which lack anterior pituitary and circulating plasma GH, and were compared with SC tissue of normal age-matched control animals. Assays were carried out for AChE and BuChE activity in the presence of their specific chemical inhibitors, BW284C51 and iso-OMPA, respectively. Results revealed that mean AChE activity was markedly and significantly reduced [28% at P21, 49% at P90, (p<0.01)] in the SC of GH deficient rats compared to age-matched controls. GH deficiency had a higher and more significant effect on AChE activity of the older (P90) rats than the younger ones (P21) ones. In contrast, BuChE activity in SC showed no significant changes in GH deficient rats at either of the two ages studied. Results imply that, in the absence of pituitary GH, the postnatal proliferation of cholinergic synapses in the rat SC, a CNS structure, where AChE activity is abundant, is markedly reduced during both the pre- and postweaning periods; more so in the postweaning than preweaning ages. In contrast, the absence of any effects on BuChE activity implies that GH does not affect the development of non-neuronal elements, e.g., glia, as much as the neuronal and synaptic compartments of the developing rat SC.
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PMID:Postnatal growth hormone deficiency in growing rats causes marked decline in the activity of spinal cord acetylcholinesterase but not butyrylcholinesterase. 2292 67

Due to the high chemical and photochemical stability, an organophosphorus pesticide triazophos might enter aquatic ecosystems and impose negative effect on aquatic organisms. In order to investigate short-term toxicity of triazophos on goldfish (Carassius auratus), antioxidant response in brain, spleen, kidney and liver was tested in this study. As a confirmation, the impact of triazophos on acetyl cholinesterase (AChE) activity was found a reduction in all studied tissues, especially in brain. In addition, 0.1 and 0.5 mg L(-1) triazophos induced MDA level increased, while glutathione content (GSH), superoxide dismutase (SOD), catalase (CAT) and lactate dehydrogenase (LDH) activities decreased. Of note, more prominent oxidative stress was provoked in kidney and liver, but weaker in brain and spleen. These results revealed that triazophos could cause a generalized oxidative stress and tissue specific antioxidant response in goldfish. Furthermore, neuroendocrine-growth-related gene expression (growth hormone (GH), luteinizing hormone (LH) and peptide YY) in brain was also changed by exposed to triazophos during 4 and 7d exposure periods. Linked with the above results, the present study pointed out that triazophos might induce a neurotoxic effect and oxidative damage in goldfish, and the goldfish brain should be a critical target for triazophos-induced damage.
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PMID:Neurotoxic effect of triazophos on goldfish (Carassius auratus) and tissue specific antioxidant responses. 2576 24

The pathological phenomenon of somatopause, noticeable in hypogonadal ageing subjects, is based on the growth hormone (GH) production and secretion decrease along with the fall in GH binding protein and insulin-like growth factor 1 (IGF-1) levels, causing different musculoskeletal, metabolic and mental issues. From the perspective of safety and efficacy, GH treatment is considered to be highly controversial, while some other therapeutic approaches (application of IGF-1, GH secretagogues, gonadal steroids, cholinesterase-inhibitors or various combinations) exhibit more or less pronounced weaknesses in this respect. Soy isoflavones, phytochemicals that have already demonstrated the health benefits in treated elderly, at least experimentally reveal their potential for the somatopausal symptoms remediation. Namely, genistein enhanced GHRH-stimulated cAMP accumulation and GH release in rat anterior pituitary cells; refreshed and stimulated the somatotropic system (hypothalamic nuclei and pituitary GH cells) function in a rat model of the mild andropause, and stimulated the GH output in ovariectomized ewes as well as the amplitude of GH pulses in the rams. Daidzein, on the other hand, increased body mass, trabecular bone mass and decreased bone turnover in the animal model of severe andropause, while both isoflavones demonstrated blood cholesterol-lowering effect in the same model. These data, which necessarily need to be preclinically and clinically filtered, hint some cautious optimism and call for further innovative designing of balanced soy isoflavone-based therapeutics.
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PMID:Somatopause, weaknesses of the therapeutic approaches and the cautious optimism based on experimental ageing studies with soy isoflavones. 2974 65


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