Insecticides Inhibiting Acetylcholinesterase

Acetylcholinesterase. Altered acetylcholinesterase less sensitive to organophosphorus and carbamate insecticides has been observed in a wide variety of insects and mites (51). Acetylcholinesterase inhibiting insecticides phosphorylate or carbamylate the serine residue in the active site of the enzyme preventing vital catalysis of acetylcholine. Resistance due to reduced sensitivity to inhibition of this target enzyme has been found in house fly, mosquitoes, green rice leafhopper, and both phytophagous and predacious species of mites. 

Acetylcholinesterase inhibition has been widely used for pesticide detection [88-94], but less exploited than protein phosphatase inhibition for cyanobacterial toxin detection. Nevertheless, the anatoxin-a(s) has more inhibition power than most insecticides, as demonstrated by the higher inhibition rates [95]. In order to detect toxin concentrations smaller than usually, mutant enzymes with increased sensitivity were obtained by genetic engineering strategies residue replacement, deletion, insertion and combination of mutations. Modifications close to the active site, located at the bottom of a narrow gorge, made the entrance of the toxin easier and enhanced the sensitivity of the enzyme. 

Tike the OP insecticides, the mode of action of the carbamates is acetylcholinesterase inhibition with the important difference that the inhibition is more rapidly reversed than with OP compounds. 

Fulton MH, Key PB. 2001. Acetylcholinesterase inhibition in estuarine fish and invertebrates as an indicator of organophosphorus insecticide exposure and effects. Environ Toxicol Chem 20 37 15. 

Tphe search for insecticides with modes of action different from the A well-known acetylcholinesterase inhibition led us to uncouplers of oxidative phosphorylation (1, 2). An inherent advantage of such pesticides would be the absence of cross-resistance with organophosphorus compounds and chlorinated hydrocarbons. The number of commercial pesticides which are likely to act by uncoupling of oxidative phosphorylation is small. All of them can be regarded as derivatives of the... 

Lein, P.J., Fryer, A.D. (2005). Organophosphorus insecticides induce airway hyperreactivity by decreasing neuronal M2 muscarinic receptor function independent of acetylcholinesterase inhibition. Toxicol. Sci. 83 166-76. 

Like other organophosphorus insecticides, the active metabolite, diazoxon, elicits toxicity by inhibiting the enzyme acetylcholinesterase in the cholinergic synapse. Acetylcholinesterase inhibition leads to accumulation of the neurotransmitter acetylcholine resulting in neurotoxicity. 

The toxicity of dichlorvos is due to inhibition of acetylcholinesterase and the signs of toxicity are generally similar to those caused by other organo-phosphorus insecticides. Dichlorvos is a direct inhibitor of cholinesterases thus, toxicity rapidly follows exposure and recovery is also rapid. With inhalation exposures, airway acetylcholinesterase inhibition is possible in the absence of significant blood enzyme inhibition. The fly head acetylcholinesterase appears more sensitive to inhibition by dichlorvos relative to mammalian brain acetylcholinesterase. At high doses, dichlorvos may cause hyperglycemia and abnormal glucose tolerance. 

Methomyl exerts toxicity by inhibiting acetylcholinesterase. As with other carbamate insecticides, acetylcholinesterase inhibition is much less persistent than with organophosphate intoxication. 

Pesticide assessment guidelines under the Federal Insecticide, Fungicide, and Rodenticide Act stipulate that organophosphates proposed for use as insecticides be tested both for their capability to cause acute toxicities due to inhibition of acetylcholinesterase and for their potential to cause inhibition of neurotoxic esterase and subsequent delayed neuropathy. Testing could be performed in laboratory rodents because they, like all species, are susceptible to acetylcholinesterase inhibition, but rodents do not develop notable ataxia, and neuropathological... 

The great majority of insecticides are nerve poisons. The target for most of them is an enzyme called acetylcholinesterase (AChE). We will describe the enzyme and its inhibition in some detail because there are no other enzymes for which we know so much about the relationship between its structure and its activity. The cholinesterase-inhibiting insecticides, the warfare gases, and the target enzyme have been the objects of intense study by scientists for many years. 

More elegant analytical methods exploit substances biological or biochemical properties. This is simple for acetylcholinesterase-inhibiting pesticides. Acetylcholinesterase is easy to measure, and the enzyme may be bought from suppliers or extracted from flies, earthworms, or vertebrate nervous tissue. The enzyme may be measured with and without addition of the extract containing the insecticide. Some plant materials may contain natural cholinesterase inhibitors (e.g., solanine in potato) that will interfere with this analysis if not removed. 

Glickman, A. H., Wing, K. D.. and Casida, J. E, (1984). Profenofos insecticide bioaciivaiion in reiatiwi to antidote action and the. slcreo,spcciriciiy of acetylcholinesterase inhibition, reactivation, and aging. Toxicol. Appl. Pharmacol. 73, 16-22. 

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