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1.
Although the molluscicide Frescon is a strong neurotoxin to the Lymnaea stagnalis central nervous system in vitro, it is probable that the exposure of the whole animal to this molluscicide fails to result in central nervous system abnormalities: Frescon does not appear to reach the brain in sufficient quantity to disrupt its normal activity. However, only those Frescon analogs found to be neurotoxic were molluscicidal, suggesting some related mode, if not site, of action. Frescon and its analogs may act by affecting excitable tissues other than the nervous system (e.g., the snail musculature) by altering certain functional and/or structural membrane properties. 相似文献
2.
The hydrolysis rates, particle sizes in suspension, and the relative lipophilicity of Frescon and its analogs were determined and compared with their neurotoxic and molluscicidal effectiveness. The hydrolysis rates of these compounds were closely correlated to their neurotoxicity, and, with one exception, to their molluscicidal effectiveness as well. The aberrant behavior of the one analog could not be attributed to a retarded penetration rate or an excessively large particle size in suspension. There appears to be some, as yet, unidentified factor which determines the molluscicidal activity of this analog. However, it is likely that both neurotoxicity and molluscicidal action are the result of a nucleophilic displacement reaction, although at different targets. Also, differences in the relative molluscicidal effectiveness of the Frescon analogs at different concentrations were possibly due to variations in particle size, which appears to be a function of the type and amount of emulsifier used. 相似文献
3.
Larry G. Hansen Elizabeth M. Cozzi Robert L. Metcalf Terry K. Hansen 《Pesticide biochemistry and physiology》1985,24(1):136-148
The oxons of leptophos, its desbromo analog, and its ethoxy analog all inhibit hen brain neurotoxic esterase (NTE) to a similar degree in vitro, but have large differences in minimum effective oral doses for organophosphorus-induced delayed neurotoxicity. The potencies of leptophos and ethoxyleptophos are increased 10-fold when administered to hens intravenously (iv), but the potency of desbromoleptophos is nearly the same whether administered iv or po. Leptophos distributes nearly five times more rapidly from the central compartment than does desbromoleptophos, and its attenuated oral potency may be due to slower net absorption and/or dilution by compartments other than nervous tissue. Intravenously administered phenylphosphonothionates are excreted rapidly into the gastrointestinal tract and a large proportion of the dose is eliminated in the first 48 hr. Indirect evidence indicates that ethoxyleptophos is more rapidly degraded and ethoxyleptophos-inhibited NTE recovers more rapidly than does NTE inhibited by leptophos or desbromomleptophos. It is proposed that differential aging of ethoxyleptophos chiral isomers as well as pharmacokinetic factors may contribute to the apparently anomalous behavior of these three analogs. 相似文献
4.
The action of the molluscicide Frescon, which induces contractures in smooth and cross-striated muscles of the freshwater snail Lymnaea stagnalis, was compared with the action of caffeine. The results indicate that the latter agent promotes contractions in Lymnaea muscles by releasing Ca2+ from intracellular stores. Such a release could not be attributed to the action of Frescon. Furthermore, the molluscicide did not appear to alter muscle function at the level of the contractile apparatus as it did not affect the time course of caffeine-induced contractions. These results favor the hypothesis that Frescon increases sarcolemmal Ca2+ permeability. 相似文献
5.
Chloride ion-selective microelectrodes were used to measure the intracellular chloride activity of Lymnaea stagnalis neurons. Values ranged from 3 to 23.5 mM in different cells. Neurons with inhibitory postsynaptic potentials had significantly lower chloride activity levels than cells without such inputs. Bicarbonate-buffered saline reduced intracellular chloride levels compared with those in Hepes-buffered saline. Frescon (Shell Chemicals) produced an increase in intracellular chloride activity in 14 out of 22 neurons (mean rate of increase, 0.09 mM/min). This increase was insensitive to changes in the membrane potential: the rate of increase was reduced in bicarbonate-buffered saline. The mechanism of Frescon action is discussed in terms of a bicarbonate/chloride exchange mechanism. 相似文献
6.
The molluscicide Frescon (N-(triphenylmethyl)morpholine) induces prolonged, irreversible contractions (contractures) in the isolated heart ventricle, penis retractor, and foot muscles of the aquatic snail Lymnaea stagnalis. It also causes contracture of the penis retractor muscle, but not the heart ventricle, of the terrestrial snail Helix aspersa. Since Frescon-induced contracture is not accompanied by a depolarization of the sarcolemma of Lymnaea heart ventricle muscle cells, it is suggested that the action of this molluscicide is associated with a membrane potential-independent activation of the contractile machinery. The rapid response of Lymnaea musculature to Frescon suggests that the direct contracture-inducing action of this molluscicide could explain its toxicity to the whole animal. 相似文献
7.
Jan Hendrik Reinders Larry G. Hansen Robert L. Metcalf Robert A. Metcalf 《Pesticide biochemistry and physiology》1983,20(1):67-75
Inhibition of chicken brain neurotoxic esterase (NTE) by a series of O-halogenated-phenyl-O-alkyl phenylphosphonates was studied in vitro. The “apparent” activity was found to consist of “true” NTE (sensitive to mipafox) plus a minor mipafox-resistant component. The pI50 of O-(2,6-dichlorophenyl) O-methyl phenylphosphonate for “true” NTE was 6.65, whereas it was about 3 for mipafox-resistant hydrolysis of phenyl valerate. This compound is suitable as an alternative to mipafox in the assay of “true” NTE, whereas the use of leptophos oxon gives a less accurate measure. The ethoxy analogs are about as potent in vitro as the corresponding methoxy compounds. Leptophosoxon and ethoxyleptophosoxon are more potent in vitro inhibitors than desbromoleptophosoxon. Within a like group of chlorinated phenylphosphonates, a reasonable correlation between in vitro neurotoxic esterase inhibition of the oxon and in vivo delayed neurotoxic potential by the corresponding phosphonothionate exists. In vivo inhibition of “apparent” NTE from chicken brain, studied 24 hr after an oral dose, is dose dependent for leptophos, ethoxyleptophos, and desbromoleptophos, the latter one being a very potent in vivo inhibitor. Ethoxyleptophos and leptophos have about equal in vivo esterase inhibitory properties. For desbromoleptophos and leptophos there is good agreement between the minimum dose causing delayed neurotoxicity and the dose leading to substantial inhibition of “apparent” NTE; ethoxyleptophos, on the other hand, inhibits the esterase at a dose much lower than the one which is neurotoxic. Several possible explanations for this discrepancy are considered. 相似文献
8.
The molluscicide Frescon induces irreversible contracture in smooth and cross-striated muscles of the freshwater snail Lymnaea stagnalis. This contracture can be inhibited or reversed by elevated Mg2+ and reduced Ca2+ concentrations, by the heavy metals Ni2+, Co2+, and Mn2+, by the rare earth La3+, and by the calcium channel blocker D-600. The removal of extracellular Ca2+ also prevents the expression of Frescon action. These results are consistent with the hypothesis that Frescon causes an increase in the Ca2+ permeability of the sarcolemma. 相似文献
9.
The sensitivity of brain acetylcholinesterase and neurotoxic esterase to inhibition by several organophosphorus compounds was studied in selected ectothermic vertebrates. These enzymes are associated with organophosphorus compound acute and delayed toxicity, respectively. In addition, the susceptibility of several of these species to delayed neurotoxicity induced by organophosphorus compounds was studied. Larvae of the gray treefrog, Southern leopard frog, and narrow-mouthed toad were exposed dermally to tri-o-tolyl phosphate or phenyl saliginen cyclic phosphate (PSCP); no symptoms of delayed neurotoxicity were observed in any of these animals up to 2 weeks after metamorphosis. No symptoms of delayed neurotoxicity were seen in juvenile bullfrogs exposed to multiple ip doses of PSCP. The specific activity of neurotoxic esterase was highest in the larval bullfrog, with juvenile channel catfish and adult mosquitofish demonstrating intermediate levels. The larval Southern leopard frog, adult Northern leopard frog, juvenile green treefrog, and adult marine toad exhibited extremely low activities. The specific activity of acetylcholinesterase was highest in the juvenile channel catfish. Neurotoxic esterase in the larval bullfrog was more sensitive to organophosphate inhibition than that in either fish. PSCP was a more potent neurotoxic esterase inhibitor than leptophos-oxon. The juvenile channel catfish had the acetylcholinesterase most sensitive to organophosphate inhibition. Under the conditions tested, no evidence of in vivo sensitivity to the organophosphate-induced delayed neurotoxicity phenomenon was observed. 相似文献
10.
The antihemolytic actions of DDT and eight analogs were examined with human erythrocytes. Apparent aqueous concentrations to produce 60% of control hemolysis ranged from 3.7 × 10?4 to 2.4 × 10?6M, with DDT being one of the least active. No correlation was found between antihemolytic potency and neurotoxicity, and it was concluded that the findings did not illuminate the toxic or neural actions of these compounds. 相似文献
11.
Thirty-eight carbamates and thiocarbamates were evaluated for the production of delayed neurotoxicity in the mature White Leghorn hen. Several thiocarbamates including phenyl-N-ethylthiocarbamate and s-2,3-dichloroallyl diisopropylthiocarbamate (diallate) produced symptoms of severe delayed neurotoxicity following repeated oral administration. The results of these experiments do not preclude the possibility that neurotoxic carbamates and organophosphorous compounds may share a common site of action. 相似文献
12.
The calcium entry blockers sodium nitroprusside (10?2M) and sodium pentobarbital (5 × 10?3M) had different effects on high-potassium-induced and Frescon-induced contractures in a smooth and a cross-striated muscle of the snail Lymnaea stagnalis. This suggests that Frescon causes an increase in sarcolemmal calcium permeability by a mechanism which is different from that utilized by high extracellular potassium. 相似文献
13.
The relative potency to target and nontarget insects of ester pyrethroids and the analogous oxime ethers, and the degree of synergism of the esters with tributyl phosphorotrithioate, provide a useful guide to the importance of esterase detoxification in species specificity. These criteria indicate that esterase detoxification is a more important component of pyrethroid tolerance in Chrysopa carnea and Cryptolaemus montrouzieri larvae than in Exochomus flavipis larvae and Musca domestica adults. Studies with 3-phenoxybenzyl 2-(4-chlorophenyl)-2-cyclopropylacetate and the corresponding 2,3,4,5,6-pentafluorobenzyl ester, their oxime ether analogs, and permethrin and its thiol ester and amide analogs provide evidence that the high insecticidal activity of some ester and E-oxime ether pyrethroids, relative to that of the corresponding thiol ester and amide, is more closely associated with the dipole moment and polarizability of the central linkage and its resistance to esterase detoxification than with bond lengths or lipophilicities conferred by a specific linkage. Pentafluorobenzyl tetramethylcyclopropanecarboxylate is very effective in the vapor state for house fly control. 相似文献
14.
Robert L. Metcalf B.Magnus Francis Robert A. Metcalf Larry G. Hansen 《Pesticide biochemistry and physiology》1983,20(1):57-66
Nineteen O-halogenated-phenyl O-methyl phenylphosphonothionates were evaluated for acute toxicity (LD50) to the female house fly Musca domestica L. and to the male Swiss white mouse, and for delayed neurotoxicity to the White Leghorn hen. The electron-withdrawing power of the phenyl substituents (Σσ? values) correlate with the LD50 values to house fly and mouse, with departures from linearity attributable to the steric hindrance of di-ortho-Cl substitution and by variations in the accessibility of the anionic site of acetylcholinesterase in the two species. The relationship with delayed neurotoxicity is less predictable although it clearly depends on suitable electron-withdrawing capacity. Delayed neurotoxicity also relates to a high degree of lipophilicity and prolonged residence time of the inhibitor in the nerve axon. 相似文献
15.
The mechanism of the entomocidal action of Bacillus thuringiensis var. israelensis (BTI) in Periplaneta americana has been studied. Cockroaches treated with the alkali-solubilized BTI crystal gradually became sluggish and immobile. A physiological examination of poisoned cockroaches indicated that BTI possessed both myotoxic and neurotoxic activity. Following hemocoel or foregut administration of BTI, myotoxic effects were observed within 10–20 min whereas the onset of neurotoxic effects was considerably delayed. The results of this study suggest that the myotoxic action of BTI is probably important for the initial manifestation of its toxicity. The neurotoxic effects of BTI were ascribed to its ability to interfere with transmitter release. BTI exerted a dual action on transmitter release in the cockroach sixth abdominal ganglion. At lower doses (2–4 μg/ml) BTI was found to suppress transmitter release by interfering with calcium uptake. At higher concentrations (12 μg/ml or higher), however, BTI caused blockage of synaptic transmission which was preceded by massive transmitter release. In either case, the synapse blocking action of BTI was probably due to its effects upon presynaptic terminals. Postsynaptic membranes and axons in the ventral nerve cord apparently remained unaffected. 相似文献
16.
The molluscicide Frescon (N-(triphenylmethyl)morpholine) induces prolonged, irreversible contractions (contractures) in the isolated heart ventricle, penis retractor, and foot muscles of the aquatic snail Lymnaea stagnalis. It also causes contracture of the penis retractor muscle, but not the heart ventricle, of the terrestrial snail Helix aspersa. Since Frescon-induced contracture is not accompanied by a depolarization of the sarcolemma of Lymnaea heart ventricle muscle cells, it is suggested that the action of this molluscicide is associated with a membrane potential-independent activation of the contractile machinery. The rapid response of Lymnaea musculature to Frescon suggests that the direct contracture-inducing action of this molluscicide could explain its toxicity to the whole animal. 相似文献
17.
The metabolic fate of six 3H-ring-substituted ethoxychlor analogs with altered aliphatic moieties and [14C]p,p′-DDT was investigated in susceptible and DDT-resistant strains of the house fly Musca domestica Linnaeus. The chloroalkane analogs, dichloroethane, chloropropane, and dichloropropane were primarily metabolized to the corresponding dehydrochlorinated products. This pathway was relatively more prominent in the resistant strain than in the susceptible strain. Biotransformation and detoxication of the isobutane, nitropropane, and neopentane derivatives was through microsomal oxidation (O-deethylation) of aryl ethoxy degradophores, and oxidation of the aliphatic moieties to produce the corresponding benzophenones, with no substantial differences between the resistant and susceptible strain. There was a strong correlation between the Taft () values for the altered aliphatic moieties of chloroalkane analogs and their rate of dehydrochlorination in both the strains. These results suggest the importance of altered aliphatic moieties in developing resistance-proof DDT derivatives. 相似文献
18.
The neurotoxic action of permethrin and chlorpyrifos on striatal dopaminergic pathways was investigated in C57BL/6 mice. Technical permethrin (50/50 ratio of cis and trans isomers, 200 mg/kg) and/or chlorpyrifos (75 mg/kg) were administered three times over a two-week period, with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20 mg/kg) given on day one. Alterations in expression of α-synuclein, dopamine transporter (DAT), and tyrosine hydroxylase (TH) were analyzed at 1 or 28 days post-treatment. MPTP alone produced a long-lasting lesion in striatal dopaminergic pathways, with a depression of TH and DAT protein at both post-treatment times. Chlorpyrifos or permethrin alone had no effect on TH or DAT expression levels. No greater effect on protein expression was observed in mice treated with both MPTP and insecticides at 1 day post-treatment. However, by day 28 a significant reduction (p < 0.05) of TH and DAT was observed in the mice treated with MPTP, permethrin, and chlorpyrifos, compared with the mice given MPTP alone. Significant alteration (p < 0.05) of α-synuclein expression by MPTP (45% decrease) and permethrin (20% increase) occurred at 1 day post-treatment, but reverted to control levels by day 28. Parallel experiments with pure cis or trans isomers of permethrin (100 mg/kg), showed that each isomer caused about half the up-regulation of α-synuclein. These findings demonstrate that the co-application of pyrethroid or organophosphorus insecticides enhance the neurotoxicity of MPTP in C57BL/6 mice, and that a slowly developing neurotoxicity may occur after termination of high-dose exposure. 相似文献
19.
Daniel D. Brown Robert L. Metcalf James G. Sternburg Joel R. Coats 《Pesticide biochemistry and physiology》1981,15(1):43-57
Forty-three DDT-type compounds were applied in saline suspension to the crural nerve of Periplaneta americana L. and the threshold concentration (ED50) to produce trains of impulses was determined together with the frequency of appearance of repetitive afterdischarge. These quantitative neurological measures were evaluated in multiple regression analyses of structural parameters including van der Waal's volume, the F and R components of Hammet's σ, and the hydrophobic constant Π. This structure-activity analysis provides an accurate estimation of the intrinsic toxicity of the DDT analogs. The results affirm previous working theories that the bulk of the functional groups within the DDT framework is the primary factor relating to activity. However, conformation is also an important parameter. 相似文献
20.
Peter Y.K. Cheung Richard M. Roe Bruce D. Hammock Charles L. Judson Mary Ann Montague 《Pesticide biochemistry and physiology》1985,23(1):85-94
Alkaline-dissolved crystal δ-endotoxin from Bacillus thuringiensis var. israelensis (serovar H 14) was injected into mice and seven species of insects representing the orders Lepidoptera, Orthoptera, Coleoptera, Hemiptera, and Diptera. High in vivo toxicity, at 1 to 5 ppm (μg toxin/g body wet wt), was observed with mice and some insects, including some that are not sensitive to the toxin when administered orally. Neuromuscular effects were observed when the toxin was injected directly into the body cavity of the test animals. Biochemical studies suggested that different protein fragments within the crystal δ-endotoxin may be responsible for the majority of the mosquito larvacidal activity and the neurotoxic symptoms observed in larvae of Trichoplusia ni. 相似文献