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)

Diagnostic electrocardiostimulation (ECS) of the right atrium with evaluation of the functional state of the heart conduction system and coronary reserve was carried out in 177 patients. The level of blood catecholamines, activity of cholinesterase and content of destroyed acetylcholine, cortisol, free fatty acids, glucose, insulin, thyroxine, triiodothyronine, renin, testosterone, calcium was determined before and at the height of diagnostic ECS. In cases with a tendency to bradycardia one could note compensatory tension of the sympathetic-adrenal system and mechanisms of general adaptation. In organic weakness of the sinus node with stable bradysystole there were signs of exhaustion of the adrenal reserves of catecholamines and cortisol manifested in paradoxic reduction of them in the blood in response to frequent ECS and corresponding changes of energy provision.
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PMID:[The neurohumoral regulation and energy support of the myocardium in patients with heart rhythm disorders]. 197 44

Stress-induced renin and prolactin secretion was investigated using a conditioned emotional response paradigm. Three minutes after placement in a chamber the rats received an electric shock to their feet via the grid floor, then were immediately returned to their home cage. This procedure was repeated for 3 consecutive days. On the fourth day, instead of receiving an electric shock, they were removed after 3 min and sacrificed by decapitation. Control rats were treated identically with the exception that shock was not administered at any time. There was a significant increase in plasma renin activity and prolactin level in the stressed rats. The administration of the antianxiety drugs chlordiazepoxide (10 mg/kg i.p.) or midazolam (0.125-2 mg/kg i.p.) blocked the stress-induced increase in prolactin levels but not the stress-induced rise in plasma renin activity. Administration of the beta-blocker propranolol (1 mg/kg i.p.) inhibited, but did not completely block, stress-induced rise in plasma-renin activity and had no effect on stress-induced prolactin secretion. The opiate antagonist naloxone (0.1-10 mg/kg i.p.) and the acetylcholinesterase inhibitor diisopropyl fluorophosphate (0.5 mg/kg i.p.) did not block stress-induced renin or prolactin secretion. It is concluded that stress-induced prolactin secretion is regulated by a benzodiazepine-mediated mechanism and that stress-induced renin but not prolactin secretion is mediated in part via beta-receptors.
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PMID:Pharmacological studies on stress-induced renin and prolactin secretion: effects of benzodiazepines, naloxone, propranolol and diisopropyl fluorophosphate. 299 44

Urinary kallikrein excretion was found as compared with 22 normal subjects (0.88 +/- 0.05 mumol/min/day) to be significantly reduced in 15 cirrhotics without ascites (0.42 +/- 0.04; p less than 0.01) and in 23 cirrhotics with ascites (0.15 +/- 0.02; p less than 0.01), and further, showed a significant difference between the two groups (p less than 0.01), but did not significantly change in 14 patients with chronic active hepatitis. Urinary kallikrein excretion in cirrhotics showed a positive correlation with serum albumin, indocyanine green disappearance rate, cholinesterase, and prothrombin, and an inverse correlation with bilirubin. After indomethacin administration to 13 cirrhotics with ascites, not only plasma renin activity and plasma aldosterone decreased significantly (p less than 0.01), but urinary kallikrein excretion also showed a small but statistically significant decrease (p less than 0.05). These results suggest that urinary kallikrein excretion decreases almost parallel to the severity of liver damage and is mediated via prostaglandins or the renin-angiotensin-aldosterone system, which may be involved in the reduction of renal blood flow in patients with liver cirrhosis.
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PMID:Urinary kallikrein excretion in chronic liver disease and effect of indomethacin. 351 May 29

Laminar patterns of cortical acetylcholinesterase (AChE) activity are reestablished in the adult, pharmacologically unmanipulated rat following axotomy of the medial cholinergic pathway. The extent to which trophic and/or growth promoting or inhibiting agents modulate AChE fiber reappearance is not fully understood. Such studies, however, would further clarify possible roles for these agents in neuronal plasticity in response to injury, as well as in plastic processes associated with normative functions. In the present experiments, we explored trophic modulation by intracortically infusing nerve growth factor (NGF) or somatostatin into cingulate cortex at a site distal to transection of the medial cholinergic pathway. Comparisons were made with sham-operated or noninfused transected controls, as well as with transected animals infused with renin or antibodies against NGF. Administration began 2 days after axotomy and continued at successive 3-day intervals for 4 weeks. It was found that, proximal to the lesion site, NGF increased and somatostatin decreased optical density of AChE; the number of AChE-containing fibers was unaltered compared to controls. Distal to the knife cut, both NGF and somatostatin increased number of AChE fibers but did not alter overall AChE optical density. Nonetheless, NGF produced an increase in the number of intensely staining puncta both proximal and distal to the cut. Neither renin nor anti-NGF antibodies produced statistically significant effects on optical density or number of fibers at any cortical locus studied. We conclude that NGF and somatostatin have opposite effects on the expression of AChE: whereas NGF increases AChE levels, somatostatin inhibits AChE accumulation in proximal fibers, perhaps by actions on synthesis or transport. Fiber proliferation, which only occurred distally, was affected positively by both NGF and somatostatin, indicating that neurite-promoting effects produced by both agents are confined to tissue regions where neurite extension is stimulated by axotomy. Increases in AChE-positive puncta produced by NGF, however, were not confined to regions of fiber proliferation.
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PMID:Trophic-factor modulation of cortical acetylcholinesterase reappearance following transection of the medial cholinergic pathway in the adult rat. 789 19

Heart failure is associated with attenuation of parasympathetic nervous function and enhanced renin-angiotensin activity. We tested whether there was a dysfunction in the efferent cholinergic neurotransmission in the heart of rats with chronic myocardial infarction (MI) and the potential role of angiotensin II (Ang II) receptors in such changes. Rats with MI and sham-operation were anesthetized, and heart rate (HR) reduction in response to vagal nerve stimulation was measured before and after losartan administration (10 mg/kg, i.v.) in the presence or absence of physostigmine to inhibit acetylcholinesterase. Infarcted rats had an average infarct size (IS) of 38% of the left ventricle (LV), depressed LV dP/dtmax, elevated LVEDP, and cardiac hypertrophy. Nerve stimulation (1-16 Hz) reduced HR in a frequency-dependent manner. The bradycardiac responses were significantly attenuated in infarcted versus control rats (p < 0.01), indicating an impaired efferent vagal tone. In contrast, the bradycardic response to exogenous acetylcholine was similar in both groups, implying an unchanged muscarinic receptor responsiveness in hearts with MI. HR response to nerve stimulation was potentiated by losartan in infarcted rats by 21 +/- 4 versus 4 +/- 2 beats/min (p < 0.01) but was unaffected in control rats. This effect of losartan was inversely related to the extent of attenuation of vagally mediated HR reduction. IS was correlated with both the extent of attenuation in vagally mediated bradycardia and the effect of losartan. In conclusion, the efferent vagal control of HR is attenuated in rats with MI and heart failure. This attenuation may be partly due to a presynaptic inhibition of acetylcholine release through the tonic activation, by Ang II, of neuronal AT1 receptors.
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PMID:Depression of efferent parasympathetic control of heart rate in rats with myocardial infarction: effect of losartan. 964 80

Vascular dementia (VAD), the second most common form of dementia after Alzheimer's disease (AD) is characterized by a cognitive deficit of cerebrovascular origin. As for AD, the main proposed treatment is based on cholinesterase inhibitors. However, randomized clinical trials (RCTs) with cholinesterase inhibitors in VAD reported modest - though sometimes statistically significant - clinical efficacy. Non-cholinergic drugs with diverse rationales and mechanisms of action have also been tested in a few RCTs for VAD; the outcomes measured are variable and the evidence of efficacy is weak. The limitations of pharmacological treatment for VAD have prompted a different strategy, i.e. primary prevention aimed at reducing vascular risk factors. Several epidemiological studies reported associations of hypertension, type 2 diabetes, obesity, and inflammation with VAD and in some cases, AD. These all coincide with those of stroke, which in turn is an established factor for cognitive decline and VAD. Here too, only a few RCTs have looked at prevention of these factors, except hypertension. Some pharmacological classes are particularly promising from the clinical and experimental viewpoints: Ca2+ channel blockers and drugs affecting the renin-angiotensin system may act independently of the effects on blood pressure. Despite some conflicting results and the need for further work, the control of risk factors might prevent cognitive decline and VAD in the elderly. The benefit of tackling vascular factors is probably larger when also considering the prevention of stroke. The objective of this review is to analyze the pharmacological treatment and prevention of VAD and their outcome. The literature on Pubmed from 1980 to 2009 was examined.
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PMID:Pharmacotherapy and prevention of vascular dementia. 2129 2

Preclinical and clinical studies indicated involvement of renin angiotensin system (RAS) in memory functions. However, exact role of RAS in cognition is still ambiguous. Our aim was to explore how angiotensin converting enzyme (ACE) modulates memory in experimental model of memory impairment. Memory deficit was induced by intracerebroventricular administration of streptozotocin (STZ, 3mg/kg) in rats. Perindopril, an ACE inhibitor, was given for 21 days and memory function was evaluated by Morris water maze test. Cerebral blood flow (CBF) was measured by laser doppler flowmetry. The biochemical and expression studies were done in cortex and hippocampus of rat brain after the completion of behavioral studies. STZ caused impairment in memory along with significant reduction in CBF, ATP level and elevated oxidative and nitrosative stress. The activity and mRNA expression of acetylcholinesterase (AChE) and ACE were also increased in rat brain regions following STZ administration. However, serum ACE activity remained unaffected. Treatment with perindopril dose dependently improved memory by increasing energy metabolism and CBF. Perindopril also decreased oxidative and nitrosative stress, activity and mRNA expression of AChE and ACE in STZ treated rat. Further, ACE inhibition mitigated STZ induced neurodegeneration as observed in histopathological studies. Moreover, perindopril per se improved memory and CBF, decreased oxidative stress with no effect on AChE activity and expression. However, perindopril per se significantly reduced ACE activity but increased mRNA expression of ACE in rat brain. These results suggest that ACE occupies a pivotal role in STZ induced memory deficit thus implicating central RAS in cognition.
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PMID:Central angiotensin converting enzyme facilitates memory impairment in intracerebroventricular streptozotocin treated rats. 2186 81

Preclinical and clinical studies indicated involvement of the central renin-angiotensin system (RAS) in memory functions. However, the role of central angiotensin-converting enzyme (ACE) in memory function is still unclear. The present study investigated the involvement of central ACE in colchicine-induced memory impairment in the context of cholinergic function and oxidative stress. Memory impairment was induced by intracerebral colchicine administration in mice. The ACE inhibitor, perindopril (0.05 and 0.1 mg/kg/day), was administered orally for 14 days. Memory function was evaluated by the Morris water maze (MWM) test from the 14(th) day on after colchicine injection. Donepezil was used as a standard. Parameters of oxidative stress and cholinergic function, ACE activity in serum and the brain were estimated after the completion of behavioral studies. Colchicine caused memory impairment as revealed by no significant change in latency to reach a hidden platform in the MWM test. Furthermore, there was a significant increase in MDA, ROS, and nitrite levels with a reduction in GSH level and acetylcholinesterase (AChE) activity in the brain of colchicine-treated mice. Colchicine significantly increased brain ACE activity without affecting serum ACE. Donepezil prevented colchicine-induced memory impairment in mice. The antidementic effect of perindopril may be attributed to reduced oxidative stress and improvement in cholinergic function. Moreover, the elevated brain ACE activity was also inhibited by perindopril. The study showed that central ACE plays an important role in colchicine-induced memory deficit, corroborating a number of studies that show that treatment with ACE inhibitors could be neuroprotective.
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PMID:Chronic inhibition of central Angiotensin-converting enzyme ameliorates colchicine-induced memory impairment in mice. 2300 12

Preclinical and clinical studies indicate involvement of renin angiotensin system (RAS) in memory functions. However, exact role of RAS in cognition is still ambiguous. The present study investigated the effects of perindopril on dementia of Alzheimer's type induced by d-galactose (d-gal) and aluminum trichloride (AlCl3). Perindopril, an angiotensin converting enzyme inhibitor, was administered intragastrically (0.5mg/kg/day) for 60days after mice were given d-gal (150mg/kg/day) and AlCl3 (10mg/kg/day) intraperitoneally for 90days. Then, memory function was evaluated by Morris water maze test. The biochemical studies were conducted in cerebral cortex and hippocampus of mouse brain after the behavioral studies. d-Gal and AlCl3 caused significant memory impairment along with significant elevation of acetylcholinesterase (AChE) activity in cerebral cortex and hippocampus. Further, a significant reduction of superoxide dismutases (SOD) and glutathione peroxidase (GSH-Px) activities, and elevation of malondialdehyde (MDA) level in cerebral cortex and hippocampus were observed. Perindopril not only improved cognitive impairment but also restored the elevation of AChE activity induced by d-gal and AlCl3. In addition, perindopril significantly increased SOD and GSH-Px activities, reduced MDA level in cerebral cortex and hippocampus. Taken together, the above findings indicate that perindopril improves learning and memorizing probably by restoring cholinergic function and attenuating oxidative damage.
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PMID:The effects of perindopril on cognitive impairment induced by d-galactose and aluminum trichloride via inhibition of acetylcholinesterase activity and oxidative stress. 2420 Oct 55

Huntington's disease (HD) is a genetic, neurodegenerative disorder mainly characterized by motor dysfunction, cognitive decline and psychiatric disturbances. 3-Nitropropionic acid (3-NP) is an inhibitor of succinate dehydrogenase (Complex II) of the mitochondrial respiratory chain, which thereby reduces production of ATP. It induces neurotoxicity by causing striatal degeneration, energy deficit and oxidative stress. Angiotensin converting enzyme (ACE) is an important protease in the renin angiotensin system (RAS) responsible for the conversion of Angiotensin I to Angiotensin II. Angiotensin-II stimulates mitochondrial oxidant release leading to depression of energy metabolism. ACE inhibitors have shown promise in disorders like stress, anxiety, and depression in addition to showing beneficial effects in cognitive disorders like Alzheimer's. Angiotensin-II inhibition enhances energy production by lowering mitochondrial oxidant production, and hence protects mitochondrial structure. Trandolapril is a centrally active ACE inhibitor. 3-NP administered systematically (20mg/kg, i.p) for 4 days consecutively induced HD like symptoms - loss of body weight, neurobehavioral alterations like memory dysfunction (elevated plus maze, Morris water maze performance), Hind-limb impairment (Narrow beam test), motor incoordination (locomotor activity). Biochemical studies on brain tissue showed increased lipid peroxidation, nitrite levels and acetylcholinesterase activity along with decreased levels of reduced glutathione, catalase activity. Mitochondrial enzyme complex activities (I, II, IV and MTT assay) were found to be significantly lowered in brain mitochondria. Administration of Trandolapril (4 and 6 mg/kg, p.o) daily for 12 days showed significant improvement in body weight, neurobehavioral parameters, oxidative stress and mitochondrial enzyme activities in rat brain. These findings were further confirmed by histopathological studies which showed improvement in 3-NP induced brain lesions. This study indicates that Trandolapril could be an effective treatment option for the management of HD.
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PMID:Potential of protease inhibitor in 3-nitropropionic acid induced Huntington's disease like symptoms: mitochondrial dysfunction and neurodegeneration. 2544 65


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