Disease relevance of Floropryl

• Heat-inactivation, diisopropylfluorophosphate, PMSF, and N-benzyloxycarbonylglycylleucylphenylalanyl-chloromethyl ketone inhibited bactericidal activity against Capnocytophaga sputigena but not Escherichia coli [1].
• We first produced the myopathy near endplates by inactivating esterases with diisopropylfluorophosphate (DFP) followed by nerve stimulation for 1--2 h in vitro [2].
• Inhibitor studies indicated that the HSV-1 protease is sensitive to the serine protease inactivator diisopropyl fluorophosphate (DFP) [3].
• Human alpha- and gamma-thrombins, as well as both bovine thrombin preparations, stimulated bone resorption in vitro, whereas catalytically inactivated human diisopropylfluorophosphate (DIP)-alpha-thrombin did not significantly stimulate resorption [4].
• The protease domain of EBV was expressed in Escherichia coli and its structure was solved by X-ray crystallography to 2.3A resolution after inhibition with diisopropyl-fluorophosphate (DFP) [5].

Psychiatry related information on Floropryl

• Administration of DFP in the preweanling period did not affect locomotor activity or pain reactivity [6].
• Resumption of daily DFP at 0.1 mg/kg caused smaller impairments of both matching accuracy and response latency [7].
• The cholinesterase inhibitor DFP facilitates the expression of paradoxical sleep (PS) propensity in rats subjected to short-term PS deprivation [8].
• Sixty percent of the variation in DFP-induced hyperthermia, a toxic response seen > 48 h after exposure, can be explained by individual differences in baseline Tc [9].
• In order to determine if there is a critical period for these effects, neonatal mice were given a single oral dose of 1.5 mg/kg DFP b.wt. on postnatal day 3, 10 or 19, causing equal inhibition of AChE [10].

High impact information on Floropryl

• The cholinesterase is found in coated vesicles of presumed endocytic origin following DFP treatment and perfusion for 3 min with galactosylated cholinesterase, a ligand for the asialoglycoprotein receptor [11].
• Experiments with diisopropylfluorophosphate thrombin and gamma thrombin demonstrate that this thrombin effect requires both receptor binding as well as catalytic activity, features consistent with the known properties of the recently characterized and cloned thrombin receptor [12].
• It has also been established that to induce the spreading reaction, the catalytic site of the Bb enzyme must be structurally intact since treatment of Bb with heat (56 degrees C for 30 min) or diisopropylfluorophosphate (10(-3) M) destroyed both enzymatic and spreading activities [13].
• Wegener's granulomatosis autoantibodies identify a novel diisopropylfluorophosphate-binding protein in the lysosomes of normal human neutrophils [14].
• Conversion by HUVEC was blocked by diisopropyl-fluorophosphate, but not by other serine protease inhibitors, including alpha 2-plasmin inhibitor [15].

Chemical compound and disease context of Floropryl

• The line of rats which were determined to be more sensitive to DFP (Flinders S line) were also more sensitive to the depressant effects of the agonists pilocarpine and physostigmine on locomotor activity, water intake, and operant responding maintained by water reward [16].
• Role of uptake of [14C]valine into protein in the development of tolerance to diisopropylphosphorofluoridate (DFP) toxicity [17].
• Instead the reduction of induced myopia could be related to the action of DFP (directly or indirectly) on dopamine levels in the retina [18].
• Protection by phenytoin and calcium channel blocking agents against the toxicity of diisopropylfluorophosphate [19].
• The objective of the present investigation was to assess the comparative efficacy of prophylactic treatment with d-tubocurarine (d-TC) (0.075 mg/kg), atropine sulfate (16 mg/kg), and atropine methylnitrate (16 mg/kg), employed singly or in combination against the diisopropylphosphorofluoridate (DFP)-induced myopathy in rat [20].

Biological context of Floropryl

• A 50-fold excess of diisopropylfluorophosphate-treated thrombin, which inhibits binding of active thrombin to endothelial cell high affinity binding sites, did not inhibit the thrombin-induced increase [21].
• Hydrolysis of diisopropylfluorophosphate with CuSO4 and imidazole virtually eliminated inhibition of thrombin, but cancer procoagulant inhibition remained complete, suggesting that cancer procoagulant was inhibited by the undefined impurity [22].
• The GPI anchors of Trypanosoma brucei variant surface glycoproteins (VSGs) undergo rounds of inositol acylation and deacylation during GPI biosynthesis and the deacylation reactions are inhibited by diisopropylfluorophosphate (DFP) [23].
• CD43 downregulation in response to opsonized zymosan, like PMA-induced CD43 downregulation, was insensitive to the serine protease inhibitor diisopropylfluorophosphate (DFP) [24].
• Treatment of PMN with DFP under conditions inhibiting proteolysis did not affect their rate of phagocytosis [25].

Anatomical context of Floropryl

• Coated vesicles isolated from rat liver perfused with diisopropylfluorophosphate (DFP) to inactivate endogenous cholinesterase contained newly synthesized secretory cholinesterase after a 30 min recovery [11].
• Polymorphonuclear leukocytes were treated with diisopropylfluorophosphate, degranulated and disrupted by nitrogen cavitation [26].
• Cytoplasmic granules from cytolytic T-lymphocytes (CTL) contain two proteins which react with the serine esterase-specific affinity label diisopropylfluorophosphate (DFP) [27].
• To determine the origin of the coated vesicle-associated AChE, we have isolated coated vesicles from cultured chick embryo myotubes which have been treated with diisopropylfluorophosphate, an essentially irreversible inhibitor of both intra- and extracellular AChE, and have been allowed to recover for 3 h [28].
• This stacking density of DFP-binding sites per surface area of membrane ( probably in the overlying sheets of basal lamina) is very similar to that in the diaphragm and sternomastoid muscles [29].

Associations of Floropryl with other chemical compounds

• This protease was preferentially localized in the smooth microsomal membrane and strongly inhibited by diisopropyl phosphorofluoridate (CAS: 55-91-4), and the optimum pH of the activity was 7 [30].
• Neither corn trypsin inhibitor (36 microM) nor diisopropylfluorophosphate (3.6 mM) diminished the effect of Factor XIIa on Fc gamma RI, although each completely inhibited the coagulant and amidolytic activity contained on the light chain of Factor XIIa [31].
• Experiments using DFP in living trypanosomes and a trypanosome cell-free system suggest that earlier GPI intermediates are also in equilibrium between their inositol acylated and nonacylated forms [32].
• When DFP is used in vivo, 400 nmol/kg cytotoxic somatostatin analog AN-238 containing AN-201 is well tolerated by mice, whereas all animals die after the same dose without DFP [33].
• Essentially identical results were obtained with active site-blocked forms of APC generated with either diisopropylfluorophosphate or D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone, which indicates that the active site was not essential for the liver association [34].

Gene context of Floropryl

• Diisopropylfluorophosphate partially inhibited shedding of TNF-R75, suggesting the contribution of a serine proteinase to the release of this receptor [35].
• The TNF-R-degrading activity in azurophil granules were identified as elastase by its sensitivity to diisopropyl fluorophosphate (DFP), alpha 1-antitrypsin and N-methoxysuccinyl-Ala-Ala-Pro-Val chloromethyl ketone (MSAAPV-CK), and by the ability of purified elastase to reproduce the effect of azurophil granules [36].
• The stimulation was inhibited by pretreatment with diisopropylfluorophosphate, PA inhibitor type 1 (PAI-1), or aprotinin, a plasmin inhibitor [37].
• Therefore, the Kd and the number of binding sites were determined by competitive inhibition curves at 4 degrees C using diisopropyl-fluorophosphate (DFP) u-PA [38].
• Our data show increased DFP-induced tremors, compensatory up-regulation of acetylcholinesterase activity, and compensatory down-regulation of M2 muscarinic receptors in the striatum of mice lacking mu-opioid receptor gene [39].

Analytical, diagnostic and therapeutic context of Floropryl

• We found, using light microscope autoradiography, that in the twitch fibers of the extraocular muscle, there is n average of 6.4 +/- 2.1 X 10(7) DFP-binding sites per endplate, of which 29% (1.8 X 10(7)) are reactivated by 2-PAM and are thus AChe [29].
• Preincubation of this conditioned medium from antibody-treated cell cultures with DFP abolished the medium's ability to mediate loss of cellular adhesion [40].
• Iodinated C3-acceptor complexes were identified by immunoprecipitation from the detergent-insoluble fraction of phagosomes prepared from DFP-treated cells ingesting S. typhimurium in the presence of 125I-Na [41].
• There was enhanced release of vWF during activated neutrophil-endothelial cell coculture; this was not inhibited by diphenyleneiodonium or by SOD plus catalase, but was inhibited by diisopropylfluorophosphate [42].
• Furthermore, treatment of BCV with DFP dramatically reduced its infectivity in a plaque assay [43].

References