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At least 325 records · Page 18Linked to original sources
PubMed1992

Genetically defined lysosomal acetylesterase EC 3.1.1.6 in the cauda epididymidis of mouse, rat, and man.

After inhibition by bis-p-nitrophenyl phosphate and subsequent staining for esterase using naphthol AS-D acetate as the substrate, a strong lysosomal esterase was demonstrated in the cauda epididymidis of mouse, rat, and man. Owing to its behaviour towards the classifying inhibitors eserine, diisopropyl fluorophosphate, bis-p-nitrophenyl phosphate, and p-chloromercuriphenylsulphonate, this lysosomal esterase was shown to be an acetylesterase (EC 3.1.1.6). Control experiments involving isoelectric focusing revealed that this acetylesterase was identical with the genetically defined homologues ES-17, ES-6, and ES-A4 in mouse, rat, and man, respectively.

4-Chloromercuribenzenesulfonate↗
PubMed1988

Triphenyl phosphite neurotoxicity in the hen: inhibition of neurotoxic esterase and of prophylaxis by phenylmethylsulfonyl fluoride.

The neuropathic syndrome resulting in the cat and the rat from single or multiple doses of the phosphorous acid ester tiphenyl phosphite (TPP) has been reported to differ from the syndrome caused by numerous phosphoric acid esters, which is known as organophosphorous compound-induced delayed neurotoxicity (OPIDN). Since the hen is used to test compounds for OPIDN, we chose to study the neurotoxicity of single subcutaneous doses of TPP using this animal model. TPP (1000 mg/kg) produced progressive ataxia and paralysis which began to develop 5-10 days after dosing. Similar signs were observed when subcutaneous doses of the OPIDN-causing agents tri-o-cresyl phosphate (TOCP) or diisopropyl phosphorofluoridate (DFP) were administered. The minimum neurotoxic dose of TPP was 500 mg/kg. Prior administration of phenylmethylsulfonyl fluoride (PMSF) prevented the development of a neuropathy induced by DFP, but did not fully protect the hens from TPP or TOCP. PMSF slowed, but did not prevent, the neuropathy caused by TOCP. PMSF reduced the neurotoxicity of 500 mg/kg TPP, but increased the neurotoxicity of 1000 mg/kg TPP. TPP was found to be a very potent inhibitor of neurotoxic esterase (NTE), the putative target site for OPIDN, in vitro, with a ki of about 2.1 x 10(5) M-1 min-1. Equimolar doses of either TPP (1000 mg/kg) and TOCP (1187 mg/kg) caused over 80% inhibition of neurotoxic esterase (NTE) in brain and sciatic nerve. This high level of NTE inhibition persisted for several weeks. This prolonged inhibition probably accounts for the inability of PMSF to block the neurotoxicity of TOCP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1977

Improved assay of neurotoxic esterase for screening organophosphates for delayed neurotoxicity potential.

The assay of neurotoxic esterase (NTE) in brains taken from dosed hens enables potential neurotoxicity of organophosphate pesticides, plasticers, etc. to be assessed. The original assay [Johnson, M.K. Biochem. J. 114, 711-717 (1969)] has been simplified to eliminate centrifugation and transfer steps and both the selectivity and the sensitivity have been increased. The procedures necessary to obtain stable reagent stocks are described.

Animals↗
PubMed1991

Prevention of diisopropylphosphorofluoridate-induced myopathy by botulinum toxin type A blockage of quantal release of acetylcholine.

Botulinum toxin type A (BTx), which blocks quantal and partially reduces spontaneous nonquantal acetylcholine (ACh) release at neuromuscular junctions, was tested for its possible attenuating effect on diisopropylphosphorofluoridate (DFP)-induced muscle lesions. The extent of muscle lesion in extensor digitorum longus and soleus muscle of DFP injected rats with and without BTx pretreatment was evaluated using light and electron microscopic procedures. In parallel experiments, acetylcholinesterase (AChE) activity was measured and the functional state of muscles in experimental groups was determined by electrophysiological methods. The results show that pretreatment with BTx almost completely protects the muscles from DFP-induced spontaneous activity and lesions in spite of critically inhibited synaptic AChE. These results are consistent with the conclusion that the effect is not mediated by direct action of organophosphate on muscle, but by the accumulation of ACh resulting in muscle hyperactivity. Therefore, it is concluded that in conditions of acutely inhibited synaptic AChE, the quantal release of ACh is essential for lesion induction, whereas the spontaneous nonquantal ACh release, which is only partially affected in BTx-blocked nerve endings, seems not to be involved.

Acetylcholine↗
PubMed1980

In vivo and in vitro inhibition of cholinesterase by methyl-1 (S methyl phosphoryl-3) imidazolium (MSPI), a model of an "instantly" aged phosphorylated enzyme.

Methyl-1 (S-methylphosphoryl-3) imidazolium (MSPI) was approximately equipotent with DFP in producing in mice a lethal intoxication and in inhibiting in vitro cholinesterases of electric-eel, brain and plasma mice. In vivo, a lethal dose of MSPI inhibited plasma but not brain ChE. The intoxication by MSPI was not cured by the combination of Atropine and TMB4 or of diazepam with Atropine and (or) TMB4 and the cholinesterase inhibition was not reversed by TMB4 in vivo nor in vitro in the conditions where DPF intoxication or Che inhibition were.

Animals↗
PubMed1980

The effects of phenylmethanesulfonyl fluoride on delayed organophosphorus neuropathy.

A delayed localized neuropathy of peripheral nerves in a single hind leg of the cat develops after a single intraarterial 2 mg/kg injection of diisopropylfluorophosphate (DFP). This neuropathy is manifested by a maximum loss of the capacity of soleus alpha-motor nerve terminals to generate stimulus-bound repetition 21 days after DFP exposure. Phenylmethanesulfonyl fluoride (PMSF) is a protective inhibitor of the neurotoxic esterase which is associated with the development of the delayed organophosphorus neuropathy. Pretreatment of cats with PMSF (30 mg/kg i.p.) 24 h before the DFP injection protected the cats from the delayed neuropathy. No clinical neurotoxic signs were observed at 21 days after DFP. The stimulus-bound repetitive capacity of soleus alpha-motor nerve terminals was not lost at this time and its incidence was much greater than that which occurred in cats not pretreated with PMSF.

Action Potentials↗
PubMed1985

Electrophysiologic changes in peripheral nerve following repeated exposure to organophosphorus agents.

The purpose of this study was to examine the electrophysiologic changes which occur following repeated exposure to potent organophosphorus agents. The results show that DFP and soman each initially increase rat sciatic nerve conduction and reduce refractoriness. Continued exposure had a diminished effect with nerve excitability eventually returning to control. During recovery, the nerve membrane responsiveness to potassium-induced depolarization significantly changed in a manner which would indicate either decreased Na, K-ATPase activity or decreased potassium ion transmembrane flux. The data suggest that compensatory changes occur in rat nerve in response to organophosphorus exposure, and further, that these compensatory changes involve alteration in membrane ion fluxes.

Action Potentials↗
PubMed1978

The anomalous behaviour of dimethyl phosphates in the biochemical test for delayed neurotoxicity.

Several dimethyl phosphate behave anomalously in tests for delayed neurotoxicity. Doses given to hens caused high inhibition of brain neurotoxic esterase (NTE) but no ataxia. Less inhibition of NTE was seen in spinal cord than in brain. Di-isopropyl phosphorofluoridate caused equal inhibition of NTE in brain and cord. When dosing with dimethyl phosphates was repeated NTE inhibition in cord increased and pair-dosed birds became ataxic. In vitro brain and cord NTE were indistinguishable but the in vivo discrepancy between inhibition of brain and cord NTE was matched by a similar discrepancy in inhibition of AChE. It appears that ataxia arises from inhibition of spinal cord NTE and that only in the present cases (among about 200) was the effect in brain not a perfect biochemical monitor.

Animals↗
PubMed1976

Therapeutic effects of some cholinolytics in organophosphate intoxications.

The therapeutic effects of pipethanate (sycotrol) and two newly synthetized cholinolytics, DPX-8 and ANC-51, were compared with atropine in mice poisoned by DDVP, fluostigmine, phospholine, and paraoxon. The antagonistic activotagonistic activity of tested drugs against acetylcholine-induced contraction of rat ileum and oxotremorine-induced salivation and tremor in the mouse was also studied. The anticholinergic activity of pipethanate, DPX-8, and ANC-51 was weaker than that of atropine. However,the therapeutic effect of pipethanate was higher than that of atropine in mice poisoned by the organophosphates. DPX-8 and ANC-51 afforded a better antidotal effect than atropine only in DDVP-poisoned mice.

Animals↗
PubMed1994

The timing of channel opening during miniature endplate currents at the frog and mouse neuromuscular junctions: effects of fasciculin-2, other anti-cholinesterases and vesamicol.

Fluctuation analysis was used to estimate the mean single-channel conductance and the mean channel duration of opening. Miniature endplate currents (MEPCs) were measured with the voltage-clamp technique. The timing of endplate channel opening during the generation of the MEPC was estimated by a deconvolution method. Often all of the channels opened during the rise of the MEPC, but in about half of the examples some 10% of the channels opened after the peak. We studied the effects of acetylcholinesterase (AChE) inhibition with neostigmine, diisopropyl fluorophosphate (DFP) and fasciculin-2. With AChE largely inhibited, the number of channels opening increased as much as fourfold, largely by channels opening in the "tail" that follows the peak of the MEPC. The results were compared to models of MEPC generation. Models did not account well for the pattern of channel opening, particularly after AChE inhibition. In the presence of fasciculin-2, the addition of 2 microM (-)-vesamicol reduced the number of channels opening and shortened the period over which channels were open. One interpretation is that quantal ACh release is not almost instantaneous, but that some of the ACh is released over a period of a millisecond or more and that some of the release is blocked by (-)-vesamicol.

Acetylcholine↗