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)

The effect of 4-methylthiophenyl dipropylphosphate (propaphos, organophosphorus insecticide) and 2-sec-butylphenyl-N-methylcarbamate (BPMC, carbamate insecticide) on the sensitivity to the effects of acetylcholine (ACh), carbachol (CCH) and nicotine was investigated on guinea-pig isolated ilea and atria. The response of these tissues to ACh was significantly enhanced in the presence of propaphos (3.3 x 10(-7) M) or BPMC (4.5 x 10(-6) M), while that to CCH was unaffected. The repeated administration of propaphos (5 mg/kg/day, p.o.) for 7 days had no effect on the contractile responses of guinea-pig ilea to potassium chloride. The responses of ilea and atria to ACh and nicotine were markedly increased by the administration of propaphos, and the values of ED50 and ED80 for their responses were significantly decreased. On the other hand, the response to CCH was decreased as was demonstrated by a significant increase in these values. Pretreatment with BPMC (25 mg/kg/day p.o., 7 days) significantly reduced the alteration in the responsiveness of the tissues to ACh, CCH and nicotine produced by the propaphos administration. The activity of cholinesterase (ChE) declined by 50--70% in blood and tissues from propaphos-treated animals, and its inhibition was significnatly reduced by the pretreatment with PBMC to 30--40%. These results indicate that changes in synaptic ChE activity, as reflected by the changes in ChE activity of blood and tissues, may be responsible for the alteration in sensitivity of ilea and atria to cholinergic agents produced by the repeated administration of propaphos and for the antagonism by BPMC.
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PMID:An alteration in sensitivity to cholinergic agents on guinea-pig ilea and atria after repeated administration of an organophosphate and an antagonism by a carbamate. 52 70

Malathion-induced marked potentiation of BPMC toxicity (about fivefold) was analyzed by measuring LD50 as an index of acute toxicity. The acute lethality of BPMC was decreased by muscarinic blockers (atropine, methylatropine, or trihexyphenidyl) or a monoamine oxidase inhibior (pargyline) and increased by a monoamine depleter (reserpine) or a dopaminergic blocker (haloperidol). The potentiation observed with BPMC and malathion was decreased by the muscarinic blockers, monoamine depleters (reserpine, alpha-methyl-p-tyrosine), an alpha-noradrenergic blocker (phentolamine), or haloperidol. The acute toxicities of other N-methylcarbamates MPMC (3,4-dimethylphenyl N-methylcarbamate), MTMC (3-methylphenyl N-methylcarbamate), NAC (1-naphthyl N-methylcarbamate), and XMC (3,5-dimethylphenyl N-methylcarbamate) were potentiated by malathion to a lesser degree than that of BPMC. Atropine protected against the lethalities of all N-methylcarbamates. Reserpine or haloperidol potentiated the lethalities of N-methylcarbamates with a similar tendency toward malathion. When the inhibitory effect of each N-methylcarbamate on brain acetylcholinesterase (AChE) was compared with its LD50, among five N-methylcarbamates BPMC had particularly strong anti-AChE activity. This characteristic of BPMC was not observed after the treatment with reserpine. These results suggest that BPMC may act not only on cholinergic nerves as an anti-AChE, but also on monoaminergic nerves which antagonize the lethal cholinergic effect. Malathion might inhibit the effect of BPMC on the monoaminergic nerves, thereby markedly potentiating the lethal effect of BPMC.
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PMID:Contribution of monoaminergic nervous system in potentiation of 2-sec-butylphenyl N-methylcarbamate (BPMC) toxicity by malathion in male mice. 356 12

Mice showed no toxic signs after a single injection of o-sec-butylphenyl methylcarbamate (BPMC, 10 mg/kg) or 2-isopropoxyphenyl-N-methylcarbamate (propoxur, 2 mg/kg). Each dose of BPMC or propoxur caused an increase in acetylcholine content and a decrease in acetylcholinesterase activity in the forebrain of mice at 10 min, followed by an almost complete recovery in the content at 60 min. Spontaneous motor activity was depressed 10 min after and recovered 60 min after, injection of BPMC or propoxur. Neither rotarod performance nor rectal temperature showed any change after injection of BPMC or propoxur. Spontaneous motor activity may therefore be a simple method for assessing small changes in the cholinergic system.
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PMID:Effects of insecticidal carbamates on brain acetylcholine content, acetylcholinesterase activity and behavior in mice. 408 84

This study was undertaken to investigate whether cholinesterase (ChE) inhibitor exerts cardiovascular collapse through non-cholinergic mechanism in halothane-anesthetized rabbits. Physostigmine and N-methylcarbamate insecticides (BPMC = 2-sec-butylphenyl methylcarbamate and PHC = propoxur = 2-isopropoxyphenyl methylcarbamate) were employed as ChE inhibitors. Intravenous injection of physostigmine produced a dose-related pressor response a few minutes after the injection. In contrast, the injection of BPMC elicited a dose-related depressor response during the injection. PHC produced a slight depressor response during the injection followed by a dose-dependent pressor response. Norepinephrine (NE)-induced pressor response was inhibited by the ChE inhibitors with the same order and magnitude as the depressor response. ECG of physostigmine or PHC was characterized by an increase in QRS voltage and a sinus bradycardia, and that of BPMC by a decrease in QRS voltage. Atropine pretreatment inhibited the pressor response, the increase in QRS voltage and the sinus bradycardia, but not the depressor response and the decrease in QRS voltage. From these observations, it is suggested that the pressor response is ascribed to the cholinergic mechanism (acetylcholine accumulation through ChE inhibition), but the depressor response may result from a non-cholinergic mechanism. It is also suggested that the difference in the cardiovascular response is determined by a balance between cholinergic and non-cholinergic activity of each ChE inhibitor.
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PMID:Cardiovascular collapse through non-cholinergic mechanism after intravenous injection of N-methylcarbamate insecticide in rabbits. 905 95

2-sec-Butylphenyl N-methylcarbamate (BPMC) is a carbamate-type cholinesterase (ChE) inhibitor with unique toxicological properties such as noncholinergic cardiovascular collapse. Effects of BPMC on L-type Ca2+ channel currents (ICa(L)) were studied in isolated guinea pig ventricular myocytes using the whole-cell patch-clamp technique, since the examination of cardiovascular responses indicated its Ca2+ antagonistic action. BPMC induced bradycardic and hypotensive responses in vivo and inhibited contraction of isolated papillary muscles (IC50 = 1.3 x 10(-4) M) in guinea pigs. BPMC produced reversible block of ICa(L) in the concentration range of 10(-4) - 10(-3) M. At test potentials between -30 mV and +20 mV, BPMC at 3 x 10(-4) M caused marked acceleration of decay rate of ICa(L) with moderate reduction of peak ICa(L) amplitude. BPMC (3 x 10(-4) M) shifted the steady-state inactivation curve to the hyperpolarizing direction by 12.7 mV. Decay rate of Ba2+ currents (IBa(L)) was also accelerated by BPMC. Fitting analysis of inactivation kinetics of IBa(L) with a two-exponential equation revealed that BPMC accelerates the slow inactivation component. At concentrations for blocking peak IBa(L) by ca. 30%, the inactivation kinetics of IBa(L) were significantly accelerated by BPMC, but merely slightly accelerated by Ca2+ channel antagonists such as diltiazem, nifedipine, or verapamil. These results indicate that BPMC, in addition to the inhibition of ChE, blocks L-type Ca2+ channels by accelerating voltage-dependent inactivation.
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PMID:A carbamate-type cholinesterase inhibitor 2-sec-butylphenyl N-methylcarbamate insecticide blocks L-type Ca2+ channel in guinea pig ventricular myocytes. 1239 23

With the expansion of agricultural areas within the Mekong River Delta in Vietnam, a concurrent, dramatic increase has occurred in agrochemical usage. To date, little consideration has been given to the negative impacts of this agricultural activity on the aquatic resources of the region. Both acute toxicity and subacute effects on brain cholinesterase (ChE) of two of the most commonly used insecticides, diazinon and fenobucarb, on adult native snakehead (Channa striata) were evaluated in a static, nonrenewable system, the environmental parameters of which, such as dissolved oxygen, water temperature, and pH, fluctuated similarly to field conditions. Four levels of insecticides, from 0.008 to 0.52 mg/L (for diazinon) and from 0.11 to 9.35 mg/L (for fenobucarb), were tested to assess the effects on the brain ChE activity of the snakehead up to 30 and 10 d for diazinon and fenobucarb, respectively. Diazinon was highly toxic to this fish species, with a 96-h median lethal concentration (LC50) of only 0.79 mg/L, and it also caused long-term ChE inhibition, with activity still significantly inhibited by 30% after 30 d for the three highest concentrations. Fenobucarb was less toxic to this species, with a 96-h LC50 of 11.4 mg/L. Fenobucarb caused more rapid ChE inhibition but also rapid recovery. The results of the present study indicate an urgent need to regulate the usage of these pesticides in the Mekong River Delta.
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PMID:Sensitivity of brain cholinesterase activity to diazinon (BASUDIN 50EC) and fenobucarb (BASSA 50EC) insecticides in the air-breathing fish Channa striata (Bloch, 1793). 1670 77

Effects of dissolved pesticides on fish are widely described, but little is known about effects of pesticide-contaminated feeds taken up orally by fish. In integrated farms, pesticides used on crops may affect grass carp that feed on plants from these fields. In northern Vietnam, grass carp suffer seasonal mass mortalities which may be caused by pesticide-contaminated plants. To test effects of pesticide-contaminated feeds on health and bioaccumulation in grass carp, a net-cage trial was conducted with 5 differently contaminated grasses. Grass was spiked with 2 levels of trichlorfon/fenitrothion and fenobucarb. Unspiked grass was used as a control. Fish were fed at a daily rate of 20% of body mass for 10 d. The concentrations of fenitrothion and fenobucarb in pond water increased over time. Effects on fish mortality were not found. Fenobucarb in feed showed the strongest effects on fish by lowering feed uptake, deforming the liver, increasing blood glucose and reducing cholinesterase activity in blood serum, depending on feed uptake. Fenobucarb showed increased levels in flesh in all treatments, suggesting bio-concentration. Trichlorfon and fenitrothion did not significantly affect feed uptake but showed concentration-dependent reduction of cholinesterase activity and liver changes. Fenitrothion showed bioaccumulation in flesh which was dependant on feed uptake, whereas trichlorfon was only detected in very low concentrations in all treatments. Pesticide levels were all detected below the maximum residue levels in food. The pesticide-contaminated feeds tested did not cause mortality in grass carp but were associated with negative physiological responses and may increase susceptibility to diseases.
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PMID:Pesticide-contaminated feeds in integrated grass carp aquaculture: toxicology and bioaccumulation. 2455 19