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

Increased incidence of renal insufficiency is observed in severe damage of liver parenchyma such as fulminant hepatitis, decompensated cirrhosis of the liver, septic cholangitis and the different forms of obstructive jaundice. Functional circulatory disturbances of the kidney, especially of the renal cortex, are of importance in the aetiology of this condition. Dopamine, at a dosage as low as 3 gamma/kg/min leads to an improvement in renal blood flow and also to an increase in hepatic blood flow. These observations are of therapeutic importance. Some important circulatory and functional parameters of both these organs, which influence each other under normal and pathological conditions, were studied in the presence of dopamine and the following results were obtained: 1. An investigation of the intrarenal haemodynamics with 133 Xenon in patients with severe cirrhosis of the liver and in patients with obstructive jaundice resulted in an increase of 91% in the mean renal blood flow. The blood flow in the renal cortex increased by 36.2% and in the renal medulla 18.5%, whereas the renal fat tissue showed no change. Compartment I, which was diminished as compared with the control value, also increased. The percentage contribution of the mean renal blood flow and the blood flow of the renal cortex towards the cardiac output was greater under the influence of dopamine; hence a greater part of the cardiac output flows into the kidney under dopamine. 2. The glomerular filtrate and the renal plasma flow increased under dopamine (13.5% and 43.1%, respectively). The increase was greater in compensated than in decompensated cirrhosis. In patients with obstructive jaundice there was a smaller increase in both these parameters than in patients with cirrhosis in the presence of dopamine. No connection was found between the increase in renal plasma flow with dopamine and the blood levels of bilirubin, cholinesterase, GOT and the Normotest. 3. The urinary output of sodium increased by 191.4% with dopamine. Patients with an initial renal plasma flow value of over 300 ml/min had a higher sodium output. These patients also eliminated more sodium under the influence of dopamine than those with an initial renal plasma flow value of under 300 ml/min. 4. Blood flow determinations in the portal vein and the hepatic artery in man, obtained during operation, showed an increase in portal flow of 28.5% and hepatic artery flow of 6.3% in response to dopamine. The percentage contribution of portal blood flow towards the cardiac output increase on dopamine administration. The functional hepatic blood flow, analyzed with 131-J-BSP, did not change. The wedged hepatic vein pressure, which is a good measure of portal pressure, increased on average by only 7% with dopamine at a dosage of 3 gamma/kg/min, but by 20.3% with twice the dosage. Dopamine did not cause a change in hepatic blood volume; hence, blood sequestration in the liver can be excluded in response to the dopamine-evoked increase in portal blood flow. 5...
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PMID:[Clinical and experimental investigations of the effect of dopamine on haemodynamics and function of kidney and liver (author's transl)]. 27 63

Changes in the cholinergic, serotonergic, noradrenergic, dopaminergic, GABAergic and somatostatinergic neurons were investigated to determine their roles in Alzheimer's disease (AD). Markers for these systems were analyzed in postmortem brain samples from 20 patients with AD and 14 controls. In the CSF study, markers for the cholinergic neurons (choline esterase, ChE) and for the somatostatinergic neurons (somatostatin-like immunoreactivity, SLI) were assayed for 93 and 75 probable AD patients and 29 and 19 controls, respectively. Activity of choline acetyltransferase (CAT) was decreased by 50-85% in four cortical areas and hippocampus in patients with AD, but not in other areas of the brain, indicating a profound deficit in the function of cholinergic projections ascending from the nucleus basalis to the cerebral cortex and hippocampus in AD. Muscarinic receptor binding was reduced by 18% in the frontal cortex but not in other areas of the brain in AD. Serotonin (5HT) concentrations were reduced (by 21-37%) in hippocampal cortex, hippocampus and striatum; and 5HT metabolite levels were lowered (by 39-54%) in three cortical areas, thalamus and putamen in AD patients. Concentrations of noradrenaline (NA) were reduced (18-36%) in frontal and temporal cortex and putamen. These data imply that serotonergic and noradrenergic projections are also affected in AD but less than the cholinergic neurons. Dopamine (DA) concentrations in AD patients were reduced by 18-27% in temporal and hippocampal cortex and hippocampus, while HVA, the metabolite of DA, was unaltered. Glutamic acid decarboxylase activity was not altered in AD. SLI was decreased (28-42%) in frontal, temporal and parietal cortex, but not in thalamus and putamen in patients with AD. Frontal tangle scores correlated most strongly with cortical CAT activity reduction and less so with decreases of 5HT, NA and DA, indicating a closer correlation with the cholinergic changes and severity of AD than with other neurotransmitter deficiencies. ChE activity and SLI were reduced by 20% and 35%, respectively, in CSF of the whole group of AD patients as compared to the controls. Comparison of CSF findings between four subgroups of dementia severity indicated that the SLI was already reduced in the group of mildest AD (-31%), while ChE activity was not. Although ChE activity in CSF declined in relation to dementia severity, however, the maximal reduction was only modest (-30%). On the other hand, SLI in CSF showed only a slight further reduction (up to -41%) as the dementia become more severe.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neurotransmitter changes in Alzheimer's disease: implications to diagnostics and therapy. 198 17

The effects of atropine and the oxime HI 6 on running performance, brain and plasma cholinesterase activity and brain catecholamines were investigated in mice intoxicated with sublethal doses of soman (100 micrograms/kg s.c.). The running time on a rotating mash wire drum (total running time 60 min) after injection of soman was reduced to 17.2 min. Treatment with atropine (10 mg/kg i.p.) or HI 6 (55 mg/kg i.p.) improved the running performance to 48.2 and 44.8 min, respectively. Cholinesterase activity was decreased in soman poisoned mice to 47.3% in plasma and 43.5% in brain. Therapy with the oxime HI 6 resulted in a reactivation of soman-inhibited peripheral cholinesterase to 76.6%, but failed to reactivate central cholinesterase. Dopamine levels in mice brain were elevated in soman poisoning by 23.2%, whereas noradrenaline levels remained unchanged. The increase in brain dopamine levels was antagonized by atropine as well as by HI 6. The results of this study lead to the speculation that central dopaminergic mechanisms may be involved in soman toxicity as well as in the antidotal action of atropine and the mainly peripherally acting oxime HI 6.
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PMID:Studies on the role of central catecholaminergic mechanisms in the antidotal effect of the oxime HI 6 in soman poisoned mice. 319 Apr 54

Continuous pressure recordings were made in guinea-pig antral pouches in vitro. The antral phasic activity was stimulated by acetylcholine and by the cholinesterase inhibitory agent physostigmine. Dopamine and isoprenaline both significantly impaired antral pressure responses to physostigmine, whereas the acetylcholine-induced response was not significantly reduced. This suggests that both dopamine and isoprenaline to some extent act by reducing the spontaneously released acetylcholine, suggesting that both drugs act on intramural cholinergic neural pathways.
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PMID:Inhibitory effects of dopamine and isoprenaline on antral motor activity stimulated by acetylcholine or physostigmine in vitro. 399 82

Neuropharmacological studies of Schistosoma mansoni were conducted in vitro using visual observations of motor activity and measurements of worm length and extracellular electrical activity. The instrumentation and methodology described quantitatively measure extracellular electrical potentials associated with motor activity, and provide a highly sensitive, objective technique for studying effects of antischistosomal compounds and for evaluating schistosomes as a model for neuropharmacological investigation. The visual motor and electrical responses of schistosomes to various pharmacological agents support earlier claims for the presence of an excitatory tryptaminergic system and an inhibitory cholinergic system. The stimulation of motor activity by 5-hydroxytryptamine was blocked by the antagonists metergoline and cyproheptadine in a dose-dependent manner. The hypermotility induced by cholinergic blockade (atropine or mecamylamine) or 5-hydroxytryptamine release (p-chlorophenylethylamine) was abolished by these antagonists. The cholinomimetic agents, acetylcholine, carbachol and arecoline, and the cholinesterase inhibitors neostigmine and metrifonate, caused a flaccid paralysis of schistosomes. Carbachol-induced paralysis was reversed by both the nicotinic cholinergic blocker, mecamylamine, and the muscarinic cholinergic blocker, atropine. This reversal occurred in a dose-dependent manner. It is suggested that the cholinoceptive site in S. mansoni has unique pharmacological properties, distinctly different from those in mammals. Dopamine, apomorphine, epinephrine and norepinephrine had little effect on schistosome motility, but produced marked increases in worm length. The dopaminergic antagonist, haloperidol, completely blocked the dopamine response. A broad range of putative amino acid neurotransmitters failed to alter schistosome motor activity. The simple nervous system of the schistosome appears to have many unique pharmacological features which may make it a useful model for the study of drugs for human use, as well as providing an effective point for chemotherapeutic attack.
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PMID:Neuropharmacology of the parasitic trematode, Schistosoma mansoni. 613 Jul 10

A microdialysis technique was used to investigate the effect of physostigmine (PHY) and heptylphysostigmine (HEP), administered systemically or locally, on the extracellular levels of acetyl-choline (ACh), norepinephrine, dopamine and 5-hydroxytryptamine in the cerebral cortex of the rat. Levels of these neurotransmitters in dialysates were assayed simultaneously with two different high pressure liquid chromatography systems. No cholinesterase inhibitor was added into the probe to increase detection of ACh after systemic administration. Cholinesterase inhibition and its relation to ACh levels were also studied. Systemic administration of two doses of cholinesterase inhibitor [PHY (30 and 300 micrograms/kg) and HEP (2 and 5 mg/kg)] produced a dose-dependent increase in ACh levels. Local perfusion of these drugs through the probe elicited a strong increase in extracellular ACh. HEP produced a longer lasting inhibition of cholinesterase and a more prolonged elevation of ACh in cerebral cortex than PHY. After systemic administration of PHY (both doses), we observed a significant increase of norepinephrine levels. This effect was weaker after HEP. Local administration through the probe did not modify norepinephrine concentration. Dopamine levels were also increased after systemic administration. ONly HEP perfused into the probe elicited a significant increase in extracellular dopamine. Systemic or local administration did not modify 5-hydroxytryptamine levels. These observations suggest a more favorable pharmacological profile for HEP as a potential drug for Alzheimer disease, as compared to PHY.
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PMID:Cholinesterase inhibitor effects on neurotransmitters in rat cortex in vivo. 791 96

The cataleptogenic effects of haloperidol, a dopamine D2 receptor antagonist; SCH23390, a D1 receptor antagonist; physostigmine, a cholinesterase inhibitor; and pilocarpine, a muscarinic M1 receptor agonist, were challenged by pretreatment of mice with SKF38393, a dopamine D1 receptor agonist; apomorphine, a dopamine D1/D2 receptor agonist (mainly D2 receptor); pirenzepine, a muscarinic M1 receptor antagonist; and scopolamine, a muscarinic M1/M2 receptor antagonist. The effect of physostigmine and pilocarpine on haloperidol and SCH23390 cataleptic responses was also examined. Each of the challenging agents blocked one or more of the cataleptogenic agents, but only scopolamine blocked all four. Pirenzepine blocked cataleptic responses induced by SCH23390 and pilocarpine, but not those by haloperidol and physostigmine. The results of this study suggest that the action of physostigmine (endogenous acetylcholine) on M2 receptors might be more potent than that on muscarinic M1 receptors. A further interesting observation was that the haloperidol-induced catalepsy was enhanced by physostigmine pretreatment, but not by pilocarpine pretreatment, whereas the SCH23390-induced catalepsy showed the opposite spectrum of enhancement by the two cholinergic agonists. We conclude that, although the four cataleptogenic agents act via the dopaminergic-cholinergic systems, their pharmacological differences may be due largely to the different receptor subtypes that are involved in the mediation of catalepsy produced by each agent. Thus, dopamine receptors not only influence the cholinergic muscarinic receptors, but muscarinic M1 and M2 receptors also might mediate dopamine D1 and D2 receptor responses, respectively. The results suggest that there are, at the least, relationships between muscarinic M1 receptors and dopaminergic D1 receptors, and between muscarinic M2 receptors and dopaminergic D2 receptors. Dopamine D1 and D2 receptors may interact in a synergistic fashion on dopaminergic systems, but act independently of each other in influencing other system such as cholinergic neurons.
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PMID:Dopaminergic and cholinergic interaction in cataleptic responses in mice. 926 77

The clinical usage of the cholinesterase inhibitor tacrine for treatment of Alzheimer's disease is accompanied by adverse effects on the gastrointestinal tract. These adverse effects are a result of the direct action of tacrine on the intestinal smooth muscles or of the modulation of certain neurotransmitters regulating gastrointestinal functions. Dopamine is a neurotransmitter that modulates gastrointestinal motility. This study was designed to examine in vitro the effects of tacrine on dopamine-induced changes in spontaneous activity of smooth muscle preparations from rat's gastric corpus. The mechanical activity was isometrically registered. Tacrine 1.10(-7)-1.10(-5) mol/l caused smooth muscle contraction, which was blocked by atropine 1.10(-6) mol/l. Tacrine 1.10(-4) mol/l provoked a relaxation resistant to atropine. Dopamine and D(2)-receptor antagonists haloperidol and R121 had no effect on tacrine-induced relaxation. Dopamine-induced contraction was concentration-dependent. It was blocked by D(2)-receptor antagonists haloperidol and R121 and by tacrine 1.10(-4) mol/l. In the presence of tacrine 1.10(-7)-10(-5) mol/l or atropine the dopamine-induced contraction was significant. The data obtained suggested that tacrine 1.10(-4) mol/l inhibited the dopamine effects on gastric corpus smooth muscles. The effect was probably not dependent on its anticholinesterase activity or not realized through direct influence on D(2)-dopamine receptors.
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PMID:Influence of tacrine on dopamine-induced reactions of the gastric smooth muscle of rats. 1507 8

Cognitive impairment in schizophrenia occurs in the early phases of the disease and remains throughout its course. The basis for cognition lies in two main brain regions: the prefrontal cortex and hippocampus. Positron emission tomography, functional magnetic resonance imaging, and proton magnetic spectroscopy studies have shown that prefrontal cortex and hippocampus activity and cell density are lower in patients with schizophrenia than in healthy controls. Dopamine remains the fundamental neurotransmitter involved with schizophrenia. Catechol- O -methyltransferase accounts for about 60% of dopamine metabolism in the prefrontal cortex. Functional polymorphism for the catechol- O -methyltransferase genotypes has been identified in patients with schizophrenia. Those with the valine-valine genotype demonstrate rapid inactivation of dopamine, and performance in cognitive testing in patients is poorer with this allele than with other genotypes. N -methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate acid receptors are also strongly associated with cognitive impairment. Changes occur in apolipoproteins D and E, cholinesterase enzyme activity, neurotensin, and neural growth factors, leading to a possible neurodegenerative process and cognitive impairment in patients with schizophrenia. A fundamental link between psychosis and neurocognition probably arises from complex interactions between these systems at the intracellular secondary messenger system and with protein phosphorylation. Atypical antipsychotics evaluated in receptor models, cell cultures, and animal behavior paradigms indicate that these agents may provide neuroprotective effects. Clinical studies with atypical antipsychotics have consistently demonstrated improvement in cognitive symptoms, and such improvement appears to be correlated with improvement of negative symptoms. A neurodevelopmental model of cognitive impairment in schizophrenia aids in understanding why atypical antipsychotics improve cognitive symptoms.
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PMID:Implications for atypical antipsychotics in the treatment of schizophrenia: neurocognition effects and a neuroprotective hypothesis. 1558 43

Although available treatments for Huntington's disease (HD) are imperfect, thoughtful application can positively impact quality of life. Dopamine antagonists can provide control of the troublesome hyperkinetic movements. These agents can also diminish the frequency of hallucinations and delusions when symptoms of psychosis occur. Classical neuroleptics have the widest utilization, although atypical antipsychotics are being increasingly used. Suppression of choreiform movements has also been reported with amantadine and tetrabenazine, which is not currently approved in the United States but under investigation. Alteration in mood can be successfully managed with a variety of antidepressant medications. Superior tolerability and value in the management of a variety of behavioral disturbances have lead to extensive use of serotonin reuptake inhibitors. Modest disturbance of mood can sometimes be addressed with anticonvulsant medications. Considered a manifestation of advanced disease, dementia is less commonly addressed therapeutically. However, gathering experience suggests improved cognitive function can occur with cholinesterase inhibitor therapy. Frequently overlooked is the value of rehabilitation services in the management of diverse symptoms. Although the value of a dysphagia evaluation is apparent, the benefit to be derived from physical and occupational therapy involvement cannot be overstated. Current therapeutic trials will undoubtedly provide additional therapies to moderate symptoms, but once the mechanism(s) of selective striatal projection neuron degeneration are delineated, a revolution in the management of HD will occur.
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PMID:Huntington's Disease. 1656 82


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