Alanine Reverses the Inhibitory Effect of Phenylalanine on Acetylcholinesterase Activity

2002 ◽  
Vol 57 (5-6) ◽  
pp. 506-511 ◽  
Author(s):  
Stylianos Tsakiris ◽  
Kleopatra H. Schulpis
Keyword(s):  
Ache Activity ◽  
Acetylcholinesterase Activity ◽  
Competitive Inhibitor ◽  
Inhibitory Effect ◽  
Electrophorus Electricus ◽  
Enzyme Stimulation ◽  
Brain Acetylcholinesterase ◽  
Competitive Activation

The aim of this work was to evaluate, in vitro, the effect of ʟ-alanine (Ala) on suckling rat brain acetylcholinesterase (AChE) and on eel Electrophorus electricus pure AChE inhibited by ʟ-phenylalanine (Phe) as well as to investigate whether Phe or Ala is a competitive inhibitor or an effector of the enzyme. AChE activity was determined in brain homogenates and in the pure enzyme after 1 h preincubation with 1.2 mm of Phe or Ala as well as with Phe plus Ala. The activity of the pure AChE was also determined using as a substrate different amounts of acetylthiocholine. Ala reversed completely the inhibited AChE by Phe (18-20% in 500-600 μᴍ substrate, p<0.01). Lineweaver-Burk plots showed that Vmax remained unchanged. However, KM was found increased with Phe (150%, p<0.001), decreased with Ala alone (50%, p<0.001) and unaltered with Phe plus Ala. It is suggested that: a) Phe presents a competitive inhibitory action with the substrate whereas Ala a competitive activation; b) Ala competition with Phe might unbind the latter from AChE molecule inducing the enzyme stimulation; c) Ala might reverse the inhibitory effect of Phe on brain AChE in phenylketonuric patients, if these results are extended into the in vivo reality.

Effect of Ethanol on Erythrocyte Acetylcholinesterase Activity

1986 ◽  
Vol 23 (4) ◽  
pp. 458-462 ◽  
Author(s):  
Nuha A Haboubi ◽  
D I Thurnham
Keyword(s):  
Ache Activity ◽  
Acetylcholinesterase Activity ◽  
Inhibitory Effect ◽  
In Vitro Experiments ◽  
Previous Exposure ◽  
Organophosphorus Poisoning ◽  
The Mean ◽  
Erythrocyte Ache ◽  
Early Indication

Erythrocyte acetylcholinesterase (AchE) activity was measured in the blood of 36 alcoholic subjects and 41 healthy volunteers. The mean activity in the alcoholics was significantly lower than that in the control subjects. In vitro experiments showed that ethanol inhibited the AchE activity immediately and in proportion to the concentration of ethanol used. Incubation times up to 6 h did not increase the inhibition significantly. Incubation of normal red cells with ethanol for 15 h, followed by washing, showed also that AchE activity was inhibited by the previous exposure to ethanol and that washing did not reduce the inhibitory effect. The possibility is considered that depressed erythrocyte AchE activity may be an early indication of potential disturbances of the autonomic nervous system. The importance of reporting ethanol intake in patients with organophosphorus poisoning is stressed.

scholarly journals In vivo and in vitro effects of fructose on rat brain acetylcholinesterase activity: an ontogenetic study

2014 ◽  
Vol 86 (4) ◽  
pp. 1919-1926 ◽  
Author(s):  
CARINE A. GUIMARÃES ◽  
MAIRIS S. BIELLA ◽  
ABIGAIL LOPES ◽  
PEDRO F. DEROZA ◽  
MARIANA B. OLIVEIRA ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Ache Activity ◽  
Young Patients ◽  
Brain Structures ◽  
Acetylcholinesterase Activity ◽  
Control Group ◽  
Inherited Disorders ◽  
Old Rats

Increased fructose concentrations are the biochemical hallmark of fructosemia, a group of inherited disorders on the metabolic pathway of this sugar. The main clinical findings observed in patients affected by fructosemia include neurological abnormalities with developmental delay, whose pathophysiology is still undefined. In the present work we investigated the in vitro and in vivo effects of fructose on acetylcholinesterase (AchE) activity in brain structures of developing rats. For the in vitro experiments, fructose was added at increasing concentrations to the incubation medium. It was observed that fructose provoked an inhibition of acetylcholinesterase activity in cerebral cortex of 30-day-old-rats, even at low concentrations (0.1 mM). For the in vivo experiments, rats were killed 1 h after a single fructose administration (5 µmol/g). Control group received the same volume of saline solution. We found that AchE activity was increased in cerebral cortex of 30- and 60-day-old rats receiving fructose administration. Finally, we observed that AchE activity was unaffected by acute fructose administration in cerebral cortex, striatum or hippocampus of 15- and 90-day-old rats. The present data suggest that a disruption in cholinergic homeostasis may be involved in the pathophysiology of brain damage observed in young patients affected by fructosemia.

Kinetics of inhibition of acetylcholinesterase by 9-hydrazino-1,2,3,4-tetrahydroacridine and 9-amino-10-methyl-1,2,3,4-tetrahydroacridinium in vitro

1980 ◽  
Vol 45 (3) ◽  
pp. 966-976 ◽  
Author(s):  
Jiří Patočka ◽  
Jiří Bajgar ◽  
Jiří Bielavský
Keyword(s):  
Rat Brain ◽  
Active Center ◽  
Active Surface ◽  
Competitive Inhibitor ◽  
Inhibitory Effect ◽  
Inhibitor Molecule ◽  
Hydrophobic Domain ◽  
Noncompetitive Inhibitor ◽  
Brain Acetylcholinesterase

The kinetics was studied of the inhibition of solubilized rat brain acetylcholinesterase by 9-hydrazino-1,2,3,4-terahydroacridine (THH) and 9-amino-10-methyl-1,2,3,4-tetrahydroacridinium (QTHA); the inhibitory effect was compared with the effect of tacrine (9-amino-1,2,3,4-tetrahydroacridine, THA). It was observed that THH is a reversible, noncompetitive inhibitor of rat brain acetylcholinesterase (Ki = 0.16 μM) and that it binds, similarly to THA, to the hydrophobic domain of the active center of acetylcholinesterase thus simultaneously inhibiting the formation of complex ES2 with acetylcholine as substrate. This eliminates the inhibition of acetylcholinesterase by an excess of substrate. QTHA is a mixed, competitive-non-competitive inhibitor characterized by KI comp = 5.3 μM and Ki noncomp = 0.08 μM. QTHA binds to an entirely different site of the active surface of acetylcholinesterase than THA and THH. This binding site is most likely the so-called β-anionic or also peripheric anionic site to which, e.g. atropine is also bound. Both inhibitors studied form with acetylcholinesterase a reversible, enzymatically inactive complex in which one inhibitor molecule is bonded to each active center of the enzyme.

scholarly journals Antimicrobial Agent Triclosan Inhibits Acetylcholinesterase Activity in Vitro in a Dose-Dependent Manner

2021 ◽  
Author(s):  
Narasimha Pullaguri ◽  
Andrea Kagoo ◽  
Anamika Bhargava
Keyword(s):  
Antimicrobial Agent ◽  
Ache Activity ◽  
Acetylcholinesterase Activity ◽  
Consumer Products ◽  
In Vivo Studies ◽  
Dependent Manner ◽  
Human Health Effects ◽  
Dose Dependent

The antimicrobial agent, Triclosan, is widely used in many consumer products. It has been designated as a "contaminant of emerging concern (CEC)" because its exposure is known to cause adverse ecological and human health effects. Triclosan is not labelled as GRAS/GRAE (generally recognized as safe and effective), but its use is still prevailing. In vivo studies have revealed that exposure to triclosan results in a decreased acetylcholinesterase (AChE) activity. However mechanistic insights into AChE inhibition by triclosan are missing. Using in vitro AChE activity assay with purified AChE, we show that triclosan acts as a direct inhibitor of AChE and inhibits AChE activity in a dose-dependent manner. Given the function of AChE, any alteration in its activity can be neurotoxic. Our results provide important mechanistic insights into triclosan induced neurotoxicity with AChE as a target.

High ammonia levels decrease brain acetylcholinesterase activity both in vivo and in vitro

1994 ◽  
Vol 22 (3) ◽  
pp. 177-184 ◽  
Author(s):  
Elena Kosenko ◽  
Yuri Kaminsky ◽  
Maria-Dolores Miñana ◽  
Santiago Grisolia ◽  
Vicente Felipo
Keyword(s):  
Acetylcholinesterase Activity ◽  
High Ammonia ◽  
Brain Acetylcholinesterase

The Effect of Barbituric Acid Derivatives on Platelet Function in Vitro and in Vivo

1973 ◽  
Vol 30 (02) ◽  
pp. 315-326
Author(s):  
J. Heinz Joist ◽  
Jean-Pierre Cazenave ◽  
J. Fraser Mustard
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Barbituric Acid ◽  
Platelet Rich Plasma ◽  
Inhibitory Effect ◽  
Primary Response ◽  
Sodium Pentobarbital ◽  
Barbituric Acid Derivatives

SummarySodium pentobarbital (SPB) and three other barbituric acid derivatives were found to inhibit platelet function in vitro. SPB had no effect on the primary response to ADP of platelets in platelet-rich plasma (PRP) or washed platelets but inhibited secondary aggregation induced by ADP in human PRP. The drug inhibited both phases of aggregation induced by epinephrine. SPB suppressed aggregation and the release reaction induced by collagen or low concentrations of thrombin, and platelet adherence to collagen-coated glass tubes. The inhibition by SPB of platelet aggregation was readily reversible and isotopically labeled SPB did not become firmly bound to platelets. No inhibitory effect on platelet aggregation induced by ADP, collagen, or thrombin could be detected in PRP obtained from rabbits after induction of SPB-anesthesia.

Inhibition of Human and Animal Platelet Adhesiveness to Glass Bead Columns by Adenosine, Dipyridamole, Chlorpromazine and Acetylsalicylic Acid

1976 ◽  
Vol 36 (02) ◽  
pp. 401-410 ◽  
Author(s):  
Buichi Fujttani ◽  
Toshimichi Tsuboi ◽  
Kazuko Takeno ◽  
Kouichi Yoshida ◽  
Masanao Shimizu
Keyword(s):  
Guinea Pig ◽  
Acetylsalicylic Acid ◽  
Guinea Pigs ◽  
Glass Bead ◽  
Animal Species ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Platelet Adhesiveness

SummaryThe differences among human, rabbit and guinea-pig platelet adhesiveness as for inhibitions by adenosine, dipyridamole, chlorpromazine and acetylsalicylic acid are described, and the influence of measurement conditions on platelet adhesiveness is also reported. Platelet adhesiveness of human and animal species decreased with an increase of heparin concentrations and an increase of flow rate of blood passing through a glass bead column. Human and rabbit platelet adhesiveness was inhibited in vitro by adenosine, dipyridamole and chlorpromazine, but not by acetylsalicylic acid. On the other hand, guinea-pig platelet adhesiveness was inhibited by the four drugs including acetylsalicylic acid. In in vivo study, adenosine, dipyridamole and chlorpromazine inhibited platelet adhesiveness in rabbits and guinea-pigs. Acetylsalicylic acid showed the inhibitory effect in guinea-pigs, but not in rabbits.

Phenolic Acids Exert Anticholinesterase and Cognition-Improving Effects

2018 ◽  
Vol 15 (6) ◽  
pp. 531-543 ◽  
Author(s):  
Dominik Szwajgier ◽  
Ewa Baranowska-Wojcik ◽  
Kamila Borowiec
Keyword(s):  
Phenolic Acids ◽  
Ex Vivo ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Amyloid Β Peptide ◽  
Beneficial Effects ◽  
Aβ Fibrils

Numerous authors have provided evidence regarding the beneficial effects of phenolic acids and their derivatives against Alzheimer's disease (AD). In this review, the role of phenolic acids as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is discussed, including the structure-activity relationship. In addition, the inhibitory effect of phenolic acids on the formation of amyloid β-peptide (Aβ) fibrils is presented. We also cover the in vitro, ex vivo, and in vivo studies concerning the prevention and treatment of the cognitive enhancement.

scholarly journals Stage-dependent effect of deferoxamine on growth of Plasmodium falciparum in vitro

Blood ◽  
1990 ◽  
Vol 76 (6) ◽  
pp. 1250-1255 ◽  
Author(s):  
S Whitehead ◽  
TE Peto
Keyword(s):  
Plasmodium Falciparum ◽  
Growth Inhibition ◽  
Antimalarial Activity ◽  
Clinical Malaria ◽  
Inhibitory Effect ◽  
Parasite Development ◽  
And Control ◽  
Speed Of Onset

Abstract Deferoxamine (DF) has antimalarial activity that can be demonstrated in vitro and in vivo. This study is designed to examine the speed of onset and stage dependency of growth inhibition by DF and to determine whether its antimalarial activity is cytostatic or cytocidal. Growth inhibition was assessed by suppression of hypoxanthine incorporation and differences in morphologic appearance between treated and control parasites. Using synchronized in vitro cultures of Plasmodium falciparum, growth inhibition by DF was detected within a single parasite cycle. Ring and nonpigmented trophozoite stages were sensitive to the inhibitory effect of DF but cytostatic antimalarial activity was suggested by evidence of parasite recovery in later cycles. However, profound growth inhibition, with no evidence of subsequent recovery, occurred when pigmented trophozoites and early schizonts were exposed to DF. At this stage in parasite development, the activity of DF was cytocidal and furthermore, the critical period of exposure may be as short as 6 hours. These observations suggest that iron chelators may have a role in the treatment of clinical malaria.

scholarly journals A novel BRD4 inhibitor suppresses osteoclastogenesis and ovariectomized osteoporosis by blocking RANKL-mediated MAPK and NF-κB pathways

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Ying Liu ◽  
Wenjie Liu ◽  
Ziqiang Yu ◽  
Yan Zhang ◽  
Yinghua Li ◽  
...  
Keyword(s):  
Bone Loss ◽  
Osteoporosis Treatment ◽  
Inhibitory Effect ◽  
Specific Gene ◽  
Actin Ring ◽  
Treatment Target ◽  
Significant Inhibitory Effect ◽  
Promising Treatment

AbstractBromodomain-containing protein 4 (BRD4) has emerged as a promising treatment target for bone-related disorders. (+)-JQ1, a thienotriazolodiazepine compound, has been shown to inhibit pro-osteoclastic activity in a BRD4-dependent approach and impede bone loss caused by ovariectomy (OVX) in vivo. However, clinical trials of (+)-JQ1 are limited because of its poor druggability. In this study, we synthesized a new (+)-JQ1 derivative differing in structure and chirality. One such derivative, (+)-ND, exhibited higher solubility and excellent inhibitory activity against BRD4 compared with its analogue (+)-JQ1. Interestingly, (-)-JQ1 and (-)-ND exhibited low anti-proliferative activity and had no significant inhibitory effect on RANKL-induced osteoclastogenesis as compared with (+)-JQ1 and (+)-ND, suggesting the importance of chirality in the biological activity of compounds. Among these compounds, (+)-ND displayed the most prominent inhibitory effect on RANKL-induced osteoclastogenesis. Moreover, (+)-ND could inhibit osteoclast-specific gene expression, F‐actin ring generation, and bone resorption in vitro and prevent bone loss in OVX mice. Collectively, these findings indicated that (+)-ND represses RANKL‐stimulated osteoclastogenesis and averts OVX-triggered osteoporosis by suppressing MAPK and NF-κB signalling cascades, suggesting that it may be a prospective candidate for osteoporosis treatment.

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