Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The irreversible cholinesterase inhibitor diisopropylphosphofluoridate (DFP) causes a naloxone-sensitive antinociceptive effect in laboratory animals. Chronic treatment of male mice with DFP (2 mg/kg/day for fourteen days) rendered the animals tolerant to its antinociceptive effect. Animals tolerant to DFP were cross-tolerant to the antinociception induced by the cholinergic agonists oxotremorine and nicotine, but no cross-tolerance with morphine was observed. Similarly, mice made tolerant to morphine were not cross-tolerant to DFP, nor were they cross-tolerant to oxotremorine and nicotine. Binding of muscarinic and nicotinic cholinergic ligands was significantly decreased in the brain of DFP-tolerant mice, due to a reduction in receptor density. No change was observed in the binding of [3H]-dihydromorphine to opiate receptors. None of these three binding sites was altered in mice tolerant to morphine. Although there is evidence of an involvement of endogenous opioids in the antinociceptive action of DFP, the lack of cross-tolerance between DFP and morphine suggests the existence of a more complex interaction between DFP and the cholinergic and opiate systems.
...
PMID:Antinociceptive effect of diisopropylphosphofluoridate: development of tolerance and lack of cross-tolerance to morphine. 299 35

We have examined the sleep profile of the Flinders Sensitive Line (FSL) of rats, which were selectively bred for supersensitive responsivity to an acetylcholinesterase inhibitor (DFP). These animals have an increased density of muscarinic receptors in striatum and hippocampus and display a number of behavioral and neuroendocrine characteristics that may represent a rodent analogue of clinical depression. A continuous 48-hour sleep EEG recording was obtained. Compared to control rats (the Flinders Resistant Line), the FSL rats had selectively more rapid-eye-movement (REM) sleep as a percentage of total sleep time. In addition, the REM sleep latency was significantly shorter and the REM-REM cycle length was significantly faster in the FSL than in the FRL strain. The two strains did not differ in total sleep time, drowsy sleep, or slow-wave sleep. The increased REM sleep in the FSL rats is consistent with the amassed evidence that cholinergic mechanisms selectively promote REM sleep, and suggests that the FSL rats may be useful in understanding the mechanism responsible for short REM latency in depression and narcolepsy.
...
PMID:Increased REM sleep in rats selectively bred for cholinergic hyperactivity. 325 94

The neurotoxicities of single doses of a chemical warfare agent VX [phosphonothioic acid, methyl-S-(2-[bis(1-methylethyl)amino/ethyl) O-ethyl ester], a metabolite of the agricultural chemical parathion, paraoxon, PO (phosphonothioic acid, diethyl paranitrophenyl ester), and the known neuropathic agents DFP] phosphorofluoridic acid, bis(1-methylethyl) ester] and TOCP (phosphoric acid, tri-o-tolyl ester) were compared in the chicken. Single injections (subcutaneous, sc) of VX as high as 150 micrograms/kg (5 times the LD50, intramuscular, im) were tolerated by laying tens if atropine and 2-pralidoxime were used as antidotes before and immediately after injection. The 150 of VX for inhibition of chicken brain acetylcholinesterase was approximately 5 X 10(-10). Plasma acetylcholinesterase, but not butyrylcholinesterase, was depressed 2 h after injections of 2-20 micrograms VX/kg im without antidotes. Levels of plasma enzymes such as creatine kinase, indicative of tissue damage, were increased after exposure to both VX and PO. Injections of up to 150 micrograms/kg of VX with antidotes did not cause locomotor or histological signs of organophosphorus-induced delayed neuropathy, but single injections of 400 mg TOCP/kg did.
...
PMID:Toxicity of an acute dose of agent VX and other organophosphorus esters in the chicken. 333 55

The present study examined the effects of a glucocorticoid and a mineralocorticoid on organophosphorus-induced delayed neuropathy (OPIDN) as previous investigations have indicated that an endogenous steroid with both properties could alter this syndrome in chickens. The glucocorticoid triamcinolone and the mineralocorticoid deoxycorticosterone were provided in the diet beginning 1 day before and continuing 10 days after triortho-tolyl phosphate (TOTP, 360 mg/kg po), phenyl saligenin phosphate (PSP, 2.5 mg/kg im), and diisopropyl phosphorofluoridate (DFP, 1 mg/kg sc). In a manner similar to that seen with corticosterone, a low concentration (0.1 ppm) of triamcinolone reduced and a high concentration (10 ppm) exacerbated clinical signs. Concentrations of deoxycorticosterone under 80 ppm also partially delayed or ameliorated ataxia induced by TOTP, PSP, and DFP, but a combination of 0.1 ppm triamcinolone and 80 ppm deoxycorticosterone was not more effective than triamcinolone alone. Peripheral nerve damage was noted in all chickens given organophosphorus compounds, whether or not they had been given corticoids. Both steroids induced hydroxylase activity, but effects on most other enzyme systems examined were unremarkable. High concentrations of triamcinolone (10 ppm) could, however, also reduce liver cytochrome P450 levels and liver cholinesterase activity. Exacerbation of OPIDN was most notable in chickens under highest stress, as indicated by elevated heterophil-to-lymphocyte ratios. The clinical, pathological, biochemical, and hematological indices of exposure to adrenocorticoids and agents inducing OPIDN in chickens were, therefore, similar for both a synthetic glucocorticoid and the endogenous steroid corticosterone.
...
PMID:Types of adrenocorticoids and their effect on organophosphorus-induced delayed neuropathy in chickens. 334 Oct 34

Memory impairment is one of the recurrent complaints of agricultural workers repeatedly exposed to organophosphorus insecticides. In an effort to establish an animal model for such behavioral effects, which would allow studying its underlying biochemical mechanism(s), in this study we evaluated spatial memory in animals following repeated organophosphate exposure. Male Long-Evans rats were given daily i.p. injections of either diisopropylfluorophosphate (DFP; 1 mg/kg/day) or disulfoton (O,O-diethyl S-[2-(ethylthio)ethyl] phosphorodithioate; 2 mg/kg/day) for 14 days. Acetylcholinesterase activity was inhibited 71-77% in the cortex, hippocampus, and striatum of rats treated with DFP, and 73-74% in those treated with disulfoton. Binding of [3H]quinuclidinyl benzilate ([3H]QNB) to cholinergic muscarinic receptors in the same brain areas was reduced 16-28% in organophosphate-treated rats. This decrease was due to a reduction in muscarinic receptor density (Bmax) with no changes in receptor affinity. At the end of the treatment rats were tested for spatial memory using the spontaneous alternation task in a T-maze. Rates of true spontaneous alternation were 64.4, 45.0, and 44.8% in animals which received corn oil, DFP, or disulfoton, respectively (P less than 0.05). These results indicate that prolonged inhibition of acetylcholinesterase caused by repeated organophosphate exposure alters spatial memory functions in rats, as well as causing a loss of muscarinic receptors. Considering the role of the cholinergic system in cognitive processes, these biochemical alterations could be related to the observed behavioral changes and may offer a potential explanation of the memory impairment reported by workers chronically exposed to organophosphates.
...
PMID:Spatial memory impairment and central muscarinic receptor loss following prolonged treatment with organophosphates. 334 Oct 49

Toxic manifestations of acetylcholinesterase inhibitors (AChE-I) include muscle twitching and muscle fiber necrosis, in addition to muscarinic manifestations of acetylcholine excess. The AChE-Is pinacolyl methylphosphonofluoridate (soman) or diisopropylphosphorofluoridate (DFP) were administered to rats to produce spontaneous muscle fiber discharges. Soman produced discharges that arose primarily from the central nervous system (CNS), while those due to DFP were generated from the peripheral nerves as well as the CNS. Three drugs were tested for their potential to reduce muscle fiber discharges: atropine methyl nitrate (AMN), ketamine, and phenytoin. Ketamine caused a significant decrease in discharges of CNS origin, while AMN and phenytoin had no effect. For muscle fiber discharges of peripheral origin, all three drugs produced a significant drop in muscle fiber discharges, but phenytoin showed slightly more efficacy than the others. AChE-I-induced muscle hyperactivity arises from actions on the CNS and on the peripheral nerve in varying proportions for different AChE-Is. Treatment for the toxicity of AChE-Is on muscle may be accomplished by administering drugs with distinctive pharmacological actions at target sites in the CNS and peripheral nervous system (PNS) where AChE-Is exert their effects. By attenuating the effects of AChE-Is at specific CNS or PNS sites, the neuromuscular toxicity can be reduced in a manner specific to the characteristic sites of toxicity of each AChE-I.
...
PMID:Effects of phenytoin, ketamine, and atropine methyl nitrate in preventing neuromuscular toxicity of acetylcholinesterase inhibitors soman and diisopropylphosphorofluoridate. 341 30

After local administration into the midbrain reticular formation of an acetylcholinesterase reactivator--Pralidoxime, a significant decrease of intensity of hippocampal theta rhythm induced by previous inhibition of acetylcholinesterase by DFP was observed already after 10 min. This result suggests that cholinergic structures are localized in midbrain reticular formation and that they play a role in the origin of hippocampal theta rhythm.
...
PMID:Effects of pralidoxime applied locally into the midbrain reticular formation on the hippocampal theta rhythm induced by acetylcholinesterase inhibition. 342 Nov 36

DFP, an irreversible acetylcholinesterase inhibitor, markedly increases spontaneous unit activity and reduces light-evoked responses in the superficial layers of the rat superior colliculus (Cheney et al., 1987). The purpose of this study was to investigate: (1) the sites of DFP action within the retino-tectal pathway (retinal, central or both), and (2) the types of cholinergic receptors (muscarinic, nicotinic, or both) involved. DFP increased SGS unit activity when injected intraocularly, confining its action to the retina, or when given systemically in bilateral enucleate rats. Thus, DFP acts at both retinal and central sites to increase unit activity in the SGS. Pretreating with muscarinic receptor antagonists such as atropine or scopolamine blocked DFP's effects at both sites whereas the nicotinic receptor antagonist mecamylamine was ineffective. Moreover, DFP's actions were mimicked by injections of the muscarinic receptor agonist, oxotremorine. The oxotremorine effects were also blocked or reversed by treatment with atropine or scopolamine. We conclude that DFP acts at both retinal and central sites to influence SGS unit activity and, at both sites, muscarinic receptors mediate DFP's effects.
...
PMID:DFP action on rat superior colliculus: localization and role of cholinergic receptors. 344 21

The effect on enkephalin degradation of the four highly potent organophosphorus anticholinesterases, soman, sarin, tabun and DFP was studied in synaptosomal fractions of rat brain striata. None of the agents effected any of the enkephalin degrading enzymes, the puromycin sensitive aminopeptidase, the p-hydroxymercurybenzoate (p-HMB) sensitive dipeptidyl aminopeptidase or the phosphoramidon sensitive enkephalinase. Furthermore, no peptidase function of acetylcholinesterase was found, when Leu-enkephalin was used as substrate at low concentrations (27 nM). Supporting the in vitro data, no difference was obtained in the striatal levels of Met- and Leu-enkephalin between rats receiving a high single dose of soman and controls. The results show that the analgesic effect of anticholinesterases are more likely due to mechanisms other than inhibition of enkephalin degradation.
...
PMID:Organophosphorus anticholinesterases do not mediate analgesia through inhibition of enkephalin degradation. 351 93

A vascularly perfused phrenic nerve-hemidiaphragm preparation from the rat was developed to study effects of physostigmine and some organophosphate inhibitors on the synthesis and release of endogenous and deuterium-labelled (choline--D9) acetylcholine (ACh) as well as the presynaptic uptake of choline. Choline and ACh were determined by combined gas chromatography/mass spectrometry. Without stimulation the endogenous levels of ACh were 320 pmole/hemidiaphragm for unlabelled and less than 1 pmole/hemidiaphragm of deuterium-labelled ACh. After stimulation at 15 Hz for 1 hr, 460 pmole/hemidiaphragm of unlabelled and 15 pmole/hemidiaphragm of deuterium-labelled ACh were found. Without stimulation the release of unlabelled ACh was 6 pmole/min/hemidiaphragm and for deuterium-labelled 0.2 pmole/min/hemidiaphragm. Evoked release (15 Hz, 1 hr) was 22 pmole/min/hemidiaphragm for unlabelled and 1.8 pmole/min/hemidiaphragm for deuterium labelled ACh. During stimulation and treatment with high concentrations (10(-5)-10(-4) M) of soman, DFP and Vx the level of unlabelled endogenous ACh increased, but the level of deuterium labelled ACh decreased in the diaphragm. During stimulation and treatment with these inhibitors the release of both unlabelled and labelled ACh decreased. During treatment with high concentrations (10(-5)-10(-4) M) of sarin and physostigmine there were no changes in endogenous levels or release of unlabelled or deuterium labelled ACh. The different effects of cholinesterase inhibitors are probably linked to the synthesis and release mechanism of ACh rather than to the choline uptake mechanism.
...
PMID:Effects of organophosphates on presynaptic events in the vascularly perfused phrenic nerve-hemidiaphragm preparation from the rat. 356 5


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---