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)

The reversibility of inhibition of plasma, red blood cell (RBC), and diaphragm cholinesterase (ChE) and clinical signs in mice given anatoxin-a(s) [antx-a(s)], a ChE inhibitor from Anabaena flos-aquae NRC-525-17, were characterized and compared with the effects of 2 known ChE inhibitors, the organophosphorus compound paraoxon and the carbamate pyridostigmine bromide. To follow recovery of ChE activity, mice were given either a control solution or an LD40 dose of one of the toxicants ip and killed at time points up to 8 d postdosing. After dosing, mice were monitored for diarrhea, fasciculations, respiratory difficulty, salivation, and tremors. In general, clinical signs in mice given antx-a(s) persisted longer than in mice given pyridostigmine and were more similar in duration to the clinical signs in mice given paraoxon. Histologic lesions were not detected in tissues of mice killed after administration of antx-a(s). Anatoxin-a(s) inhibited lesions were diaphragm ChE for greater than 1 but less than 2 d and RBC ChE for 8 d. The time required for recovery from Antx-a(s)-induced inhibition of ChE in plasma, RBC, and diaphragm was similar to or longer than that with paraoxon and longer than that with pyridostigmine. Based on the duration of antx-a(s) induced clinical signs and ChE inhibition in mice, antx-a(s) appears to be an in vivo irreversible inhibitor of ChE.
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PMID:Reversal of cholinesterase inhibition and clinical signs and the postmortem findings in mice after intraperitoneal administration of anatoxin-a(s), paraoxon or pyridostigmine. 201 58

The effects of anatoxin-a(s) [antx-a(s)] from the cyanobacterium Anabaena flos-aquae NRC-525-17 on mean arterial blood pressure, heart rate, respiratory rate, tidal volume, minute volume, and phrenic nerve activity were evaluated in anesthetized Sprague-Dawley rats. Anatoxin-a(s) was administered by continuous intravenous infusion. The initial effect of the toxin was to slow the heart rate and reduce arterial blood pressure, followed by much more pronounced reductions in these parameters. The marked decline in heart rate and blood pressure frequently occurred before there was a large decrease in respiratory minute volume [reduced by only 15.4 +/- 3% (mean +/- S.E.) compared to the predose period], suggesting that antx-a(s) has an important muscarinic action on the cardiovascular system in vivo. Phrenic nerve amplitude increased, but, nevertheless, tidal and minute volumes decreased progressively, indicating that antx-a(s), unlike most low-molecular-weight organophosphorus cholinesterase inhibitors, does not have any remarkable inhibitory action on central mediation of respiration.
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PMID:Effect of anatoxin-a(s) from Anabaena flos-aquae NRC-525-17 on blood pressure, heart rate, respiratory rate, tidal volume, minute volume, and phrenic nerve activity in rats. 251 95

Adult male Long-Evans rats were injected intraperitoneally with 1.5, 3.0 or 9.0 micrograms/kg of anatoxin-a(s) that had been extracted from laboratory-grown Anabaena flos-aquae NRC-525-17, 800 micrograms/kg of paraoxon, or a control solution. Blood, anterior spinal cord, and brain cerebellar, cortical, medullary, midbrain, hippocampal, hypothalamic, olfactory and striatal cholinesterase activity was determined in rats that died prior to 2 hours or were anesthetized and killed at 2 hours. Unlike paraoxon, anatoxin-a(s) did not cause detectable inhibition of cholinesterase in the central nervous system, but did cause inhibition of cholinesterase in blood, suggesting that anatoxin-a(s) is strictly a peripheral cholinesterase inhibitor.
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PMID:Regional brain cholinesterase activity in rats injected intraperitoneally with anatoxin-a(s) or paraoxon. 281 13

Anatoxin-a(s) [antx-a(s)] is produced by Anabaena flos-aquae clone NRC 525-17 and is different from anatoxin-a, a known depolarizing agent produced by A. flos-aquae NRC 44-1. Purification of antx-a(s) from lyophilized cells involved extraction with 1.0 M acetic acid: ethanol (80:20), column chromatography (Sephadex G-15 and CM-Sephadex C-25) and high performance liquid chromatography. Purified toxin has an LD50 (i.p., mouse) of approximately 50 micrograms/kg. Gross pharmacological tests of antx-a(s) on isolated chick biventer cervicis and frog rectus abdominis muscles showed no direct agonistic effect. Instead, antx-a(s) augments the acetylcholine response and antagonizes the actions of d-tubocurarine. Twitch potentiation and tetanic fade were observed on isolated rat phrenic nerve--diaphragm muscle when stimulated indirectly at different frequencies. In acute toxicity tests with mice and rats the signs of poisoning were indicative of excessive cholinergic stimulation. Mice pretreated with atropine sulfate showed longer survival times and no parasympathomimetic signs of toxicity. The mice still died of respiratory arrest with convulsions, which indicated that toxicity is due to more than just the peripheral muscarinic action of antx-a(s). Assays of serum cholinesterase of rats in acute toxicity tests showed complete inactivation of the enzyme at doses of 350 and 600 micrograms/kg. It was concluded that antx-a(s) may be acting as an anticholinesterase, thereby causing toxicity.
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PMID:The pharmacology of anatoxin-a(s), a neurotoxin produced by the freshwater cyanobacterium Anabaena flos-aquae NRC 525-17. 308 30

Anatoxin-a(s), an alkaloid neurotoxin from the freshwater cyanobacterium, Anabaena flos-aquae NRC-525-17, was compared to paraoxon, physostigmine and pyridostigmine for effects on brain cholinesterase after i.p. injection into Balb/c mice. The duration of clinical signs in mice injected with anatoxin-a(s) persisted longer than in mice given the carbamates and was comparable with that of paraoxon. Anatoxin-a(s) did not inhibit brain cholinesterase activity suggesting that this toxin is unable to cross the blood-brain barrier.
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PMID:Comparison of effects of anatoxin-a(s) and paraoxon, physostigmine and pyridostigmine on mouse brain cholinesterase activity. 318 65