Gene/Protein Disease Symptom Drug Enzyme Compound
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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The two parameters of the active [methyl-3H]choline uptake into isolated rat forebrain microvessels, Km and Vmax, were determined for 1-, 3-, 10-, and 24-month-old Charles River male rats and compared with the activities of the enzymes choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) in these microvessels over the same time course. The value of Km remained constant over the entire period, but that of Vmax increased from 8.5 +/- 1.0 to 80.6 +/- 16.4 nmol g-1 (mean +/- SEM) over the first 3 months of life. Over the same period, the increase in ChAT activity, from an initial value of 7.1 +/- 1.6 to 10.2 +/- 0.3 nmol g-1 min-1, was not proportional to that of choline uptake. Levels of BuChE activity (0.9-1.3 mumol g-1 min-1) were almost unchanged throughout the entire 24-month period, but those of AChE showed a steady and significant increase from 1 to 24 months, remaining relatively high at senescence (4.7 mumol g-1 min-1), when choline uptake had decreased to one-third of its optimal value. Selective inhibition of AChE with 1,5-bis(4-allyldimethylammonium-phenyl)pentan-3-one dibromide (0.5 microM) in unruptured capillaries from 3-month-old rats resulted in a decrease in Vmax of choline uptake from approximately 81 to 59 nmol g-1 min-1 or with 9-amino-1,2,3,4-tetrahydroacridine (10 microM) in capillaries from 2-month-old rats from approximately 30 to 15 nmol g-1 min-1. Selective inhibition of BuChE with tetraisopropyl pyrophosphoramide (100 microM) resulted in an increase in Vmax from approximately 81 to 96 nmol g-1 min-1. It is possible that the two vascular enzyme systems are coupled to a hypothetical endothelial choline transporter, but with an action opposite to each other.
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PMID:Vascular cholinesterases and choline uptake in isolated rat forebrain microvessels: a possible link. 274 36

Mivacurium chloride (BW B1090U) is a new, short-acting non-depolarizing neuromuscular blocking agent. It is a synthetic bis-benzylisoquinolinium diester, which is hydrolysed rapidly by plasma cholinesterase. This study compares mivacurium, atracurium and vecuronium by continuous i.v. infusion. The duration of mivacurium infusion ranged from 29.5 to 286 min. The steady state infusion rates necessary to maintain 95 (SEM 4)% twitch suppression were: mivacurium 8.3 (0.7) micrograms kg-1 min-1; atracurium 7.9 (0.4) micrograms kg-1 min-1; vecuronium 1.2 (0.3) micrograms kg-1 min-1. Following infusions of mivacurium, various recovery times (for example: 25-75%, 6.9 (0.3) min; 25-95%, 11.0 (0.4) min; 5-95% 14.5 (0.4) min) did not differ significantly from those following single bolus doses. Recovery times following cessation of mivacarium infusions were approximately 50% of those for equivalent durations of infusion of atracurium (10.9 (0.3) min for 25-75% recovery and 26.6 (0.4) min for 5-95% recovery). For vecuronium, corresponding recovery times were 13.8 (0.9) and 32.0 (1.2) min, respectively. Comparative recovery times for mivacurium were 40-50% of those for vecuronium. There was a significant correlation between the infusion rate of mivacurium required to maintain 95% twitch depression and the plasma cholinesterase activity of individual subjects.
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PMID:Clinical pharmacology of mivacurium chloride (BW B1090U) infusion: comparison with vecuronium and atracurium. 290 43

Blood samples were drawn from 10 ASA physical status 1 and 2 patients before (baseline) and after the administration of cimetidine to determine the in vivo effect of cimetidine on plasma cholinesterase (PCHE) activity. The in vitro effects of cimetidine at different plasma concentrations were also studied using the same blood samples. PCHE activity in the baseline samples was 432 +/- 4.6 (mean +/- SEM) U/ml, the dibucaine number 82. Administration of oral cimetidine (300 mg) the night before and 2 hours before surgery, failed to have any effect on PCHE activity (no in vivo effect). Plasma cholinesterase activity in the presence of cimetidine in vitro at plasma concentrations of 1.5, 15, 150, and 1500 micrograms/ml was 428, 420, 397, and 177 U/ml, respectively. Thus, in vitro data showed that cimetidine at plasma concentrations (1.5 to 15 micrograms/ml) achieved with clinical doses also has no effect on PCHE activity.
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PMID:Cimetidine does not affect plasma cholinesterase activity. 333 48

Human ejaculates were divided into 3 groups (I, II and III) according to the extent of their coagulation and the levels of free choline and cholinesterase were determined together with seminal vesicular N-acetylamino sugar and prostatic (zinc) marker components. Coagulation was determined as the percent coagulum (CG) at 5 min after ejaculation. The mean (+/- SEM) values for CG at 5 min in groups I, II and III were 6 +/- 2, 43 +/- 4 and 79 +/- 2, respectively. The time for 100% liquefaction in the 3 groups were 4.7 +/- 0.8, 12.9 +/- 1.4 and 19.1 +/- 2.1 min, respectively. Group III had significantly higher levels of choline and cholinesterase activity than groups I and II. The choline level was correlated significantly (r = 0.58) with the concentration of N-acetylamino sugar, but there was no correlation with the level of zinc. Evaluation of the level of choline in prostatic fluid, in semen from azoospermic men and in ejaculates with different CG values suggested that the level of choline may provide valuable information about activity of the seminal vesicles. Release of choline in group I was only 33 and 50% of that groups III and II, respectively. 60% of the total release of choline occurred during the liquefaction phase. The mean activity of cholinesterase in the prostate was only 27% lower than that found in seminal plasma. The liquefaction time and the concentration of choline, N-acetylamino sugar and zinc decreased significantly in ejaculates after 2 days of abstinence.
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PMID:Grouping of human ejaculates according to the degree of coagulation and the relationship to the levels of choline and cholinesterase. 357 May 33

Long-Evans male adult rats were intermittently exposed for 14 weeks to continuous wave (CW) 2450-MHz microwaves at an average power density of 2.5 mW/cm2. The mean specific absorption rate was 0.70 W/kg (+/- 0.02 SEM). The rats were exposed 7 h/day, 7 days/week in a radiation chamber with a monopole above ground, while housed in Plexiglas cages. Weekly measures of body mass and food intake did not indicate statistically significant effects of microwave irradiation. Assessments of threshold for electric-footshock detection revealed a significant difference between microwave and sham-exposed animals. Assessments of cholinesterase and sulfhydryl groups in blood and 17-ketosteroids in urine did not distinguish the two groups of rats. Behavioral measures made at the end of the 14-week exposure included an open-field test, shuttlebox avoidance performance, and schedule-controlled lever-pressing for food pellets. Statistically significant differences between microwave- and sham-exposed rats were observed for these measures. Examination of adrenal tissue, plasma electrolytes, and organ masses after 14 weeks of exposure revealed no difference between the two groups of rats.
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PMID:Intermittent exposure of rats to 2450 MHz microwaves at 2.5 mW cm2: behavioral and physiological effects. 375 34

To determine the neurotoxic effects of organophosphorus compounds in turkeys, adult birds were given a single oral dose of 125, 250, 500 mg/kg triorthotolyl phosphate (TOTP) or a single subcutaneous dose of 0.4 mg/kg O,O'-diisopropyl phosphorofluoridate (DFP). At 24 h after dosing with TOTP, neurotoxic esterase activity was found to be inhibited in a dose-related manner, as were the activities of blood cholinesterase and liver cholinesterase. Clinical signs of neuropathy appeared within 2 wk in TOTP-treated groups of birds with neurotoxic esterase activities at 59 +/- 3% (125 mg/kg), 47 +/- 7% (250 mg/kg) and 33 +/- 3% (500 mg/kg) of control values (mean +/- SEM, n = 5) at 24 h after dosing. Signs appeared earlier in turkeys given DFP. Histological examination revealed only mild lesions of delayed neurotoxicity in birds given either TOTP or DFP.
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PMID:Effect of neurotoxic organophosphorus compounds in turkeys. 395 18

Pyridostigmine 0.143 mg kg-1 (maximum 10 mg) and atropine 0.0143 mg kg-1 (maximum 1 mg) were administered i.v. to six healthy male volunteers. Peripheral venous blood samples were drawn for measurement of serum cholinesterase activity. Maximum inhibition of the enzyme was found 5 min after injection with a decrease to 27 +/- 5% (mean +/- SEM) of the original activity. Forced expiratory volume in the first 1s (FEV1) was measured at fixed time intervals for 90 min. No decrease in FEV1 was observed; on the contrary, there was a small increase. We conclude that atropine effectively antagonizes the muscarinic side-effects of pyridostigmine on bronchial smooth muscle tone and bronchial secretions, when administered in clinical doses to normal human subjects.
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PMID:Effect of a mixture of pyridostigmine and atropine on forced expiratory volume (FEV1), and serum cholinesterase activity in normal subjects. 397 Aug

Acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and alpha-fetoprotein (AFP) were measured in 293 amniotic fluids from the second and third trimesters of pregnancy in a prospective study of their diagnostic value in the detection of neural-tube defects (NTD). In normal samples, the mean AChE and BChE concentrations were 3.0 u/L (SEM = 9.1 u/L) and 15.2 u/L (SEM = 1.2 u/L) in the second trimester, and 1.6 u/L (SEM = 0.1 u/L) and 7.8 u/L (SEM = 0.6 u/L) in the third trimester. AFP levels fell throughout the second trimester to unmeasurable levels in the third. AChE levels were markedly elevated in samples from NTD pregnancies at all gestational ages, and a cut-off level of the mean + 3 SD optimally separated normal from abnormal samples. This cut-off correctly predicted 10 of 11 fetuses with neural lesions; there were three false positive results. A similar cut-off for AFP predicted nine of 11 cases of neural lesion with two false positive results. For BChE, a cut off of 50 u/L predicted eight of 11 neural lesions with two false positive results. The specificity, sensitivity, and predictive value positive (PVP) were calculated for each test. The assays of AFP and AChE were useful when used individually (PVP congruent to 80%), but a Bayesian combination of these two tests produced a superior PVP (98%). Because the cost of AChE assay is low, and the test is so simple, it is suggested that an AChE analysis should be performed whenever an amniocentesis is requested for the diagnosis of NTD.
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PMID:Combined analysis of acetylcholinesterase and alpha-fetoprotein improves the accuracy of antenatal diagnosis of neural-tube defects. 616 40

Eptastigmine is a long-lasting acetyl-cholinesterase inhibitor, currently being developed for the symptomatic treatment of Alzheimer's disease. In the present study, we investigated the relationship between pharmacokinetics and pharmacodynamics of eptastigmine in young healthy volunteers. Eight male subjects received single oral doses of 10, 20, and 30 mg of eptastigmine and placebo according to a double-blind, randomized, crossover design. Blood was collected before and 0.5, 1, 1.5, 2, 3, 4, 6, and 24 hours after drug administration. Cholinesterase activity was measured using a potentiometric method in both plasma (butyryl-cholinesterase) and in red blood cells (acetyl-cholinesterase). Eptastigmine plasma levels were measured by a very sensitive high-performance liquid chromatography method (limit of quantitation 0.2 ng/mL). Eptastigmine plasma concentrations increased proportionally with the dose (mean +/- SEM AUC0-24 was 0.74 +/- 0.58, 3.61 +/- 1.15, and 6.25 +/- 1.51 ng.h/mL with 10, 20, and 30 mg, respectively) and were undetectable at 24 hours. The inhibition of acetyl-cholinesterase was dose-dependent (peak inhibition was 15 +/- 2%, 30 +/- 4%, and 36 +/- 6% with 10, 20, and 30 mg, respectively) and long-lasting, with a residual inhibition of 8 to 11% at 24 hours. Acetyl-cholinesterase inhibition and drug plasma levels were related over time with a counterclockwise hysteresis curve, suggesting the formation of active metabolites and/or a slow association to and dissociation from the enzyme in red blood cells. Butyryl-cholinesterase inhibition was weak and not dose-dependent (peak inhibition was 12 +/- 4%, 13 +/- 3%, and 12 +/- 2% with 10, 20, and 30 mg, respectively). The drug was well tolerated by all subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship between pharmacokinetics and pharmacodynamics of eptastigmine in young healthy volunteers. 760 18

The effects of the centrally acting cholinesterase (ChE) inhibitors, tetrahydroaminoacridine (THA) and E2020 (1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl] methylpiperidine hydrochloride), potential drugs for the treatment of senile dementia, on the basal extracellular acetylcholine (ACh) concentration in the hippocampus of freely moving rats, were determined using a microdialysis technique without the use of a ChE inhibitor in the perfusion fluid and a sensitive RIA. The mean (+/- SEM) basal ACh content in the perfusate was 103.1 +/- 3.6 fmol/sample collected over 30 min when microdialysis probes with a length of 3 mm dialysis membrane were used. The content of ACh decreased to an almost undetectable level upon perfusion of magnesium, suggesting that, in the present study, most of the ACh detected in the perfusates was due to cholinergic neuronal activity. THA (1.65 mg/kg, i.p.) produced an insignificant increase in the extracellular ACh concentration, but a dose of 5 mg/kg, i.p. caused a prolonged and significant 5.5-fold increase from the control value. E2020 (0.65 and 2 mg/kg, i.p.) produced significant, prolonged and dose-dependent increases (4 and 12 times the control value, respectively), the peak effect occurring within 1 h. Perfusion with 10 mumol/l physostigmine produced an about 30-fold increase of ACh output, suggesting that the basal extracellular ACh concentration is highly dependent on ChE activity. When ChE was inhibited locally by perfusion with physostigmine, THA (5 mg/kg) produced a transient and, at its maximum, a 1.42-fold increase in extracellular ACh concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of the centrally acting cholinesterase inhibitors tetrahydroaminoacridine and E2020 on the basal concentration of extracellular acetylcholine in the hippocampus of freely moving rats. 787 Jan 92


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