Action of cismethrin and deltamethrin on functional attributes of isolated presynaptic nerve terminals from rat brain

Isolated presynaptic nerve terminals (synaptosomes) prepared from rat brain were used to evaluate the actions of a tremor (T)-syndrome (cismethrin) and a choreoathetosis-salivation (CS)-syndrome (deltamethrin) pyrethroid on the functional attributes of synaptosomes by measuring calcium influx and endogenous neurotransmitter (l-glutamate) release with fluorescent assays. Both cismethrin and deltamethrin stimulated calcium influx, however, only deltamethrin enhanced Ca²⁺-dependent neurotransmitter release and its action was stereospecific, concentration-dependent, stimulated by depolarization, unaltered by tetrodotoxin, and blocked by ω-conotoxin GVIA. Our results delineate a separate action of deltamethrin on presynaptic nerve terminals from that elicited by cismethrin and implicate Ca_v2.2 calcium channels as target sites for deltamethrin that is consistent with the observed in vivo release of neurotransmitter at the onset of convulsive symptom caused by CS-syndrome pyrethroids. This information will allow a more complete understanding of the molecular and cellular nature of pyrethroid-induced neurotoxicity and expands our knowledge of the structure–activity relationships of pyrethroids in regards to their action on voltage-sensitive calcium channels.     

Action of deltamethrin on the calcium/calmodulin-dependent protein kinase from the rat brain

The action of deltamethrin on the calcium/calmodulin-dependent protein kinase (CaM-Kinase II) and phosphatase system in the rat brain synapse was studied under various experimental conditions to optimize these enzyme activities and to facilitate the studies of the mechanism of interaction of this pesticide with several components of this enzyme system. To obtain a clear-cut inhibition of this enzyme by deltamethrin the following conditions must be met: (a) the enzyme system should be purified by precipitation with ammonium sulfate (450 g litre^?1) prior to the addition of deltamethrin, (b) both Ca²⁺ and calmodulin (CaM) should be added to the incubated media before the addition of [y-³²P]ATP, (c) deltamethrin should be incubated at least 10 min (but less than 30 min) with the enzyme system before [y-³²P]ATP addition, (d) the incubation temperature should be above 20°C (optimum 30°C), (e) [y-³²P]ATP concentration should be in the order of 10^? M (concentration adjusted using cold ATP), and (f) the incubation time with [y^?P]ATP for incorporation of ³²P into the protein should be in the neighborhood of 60 s. Under these conditions, the inhibitory potency of various active and inactive isomers or analogs of pyrethroids and DDT was tested. The order of the inhibitory power of these active forms of pesticides was 1 R-deltamethrin > (S)(RS) fenvalerate ≥ p,p′-DDT. Other compounds were not active at the concentration tested, indicating the differential sensitivity of this enzyme and the existence of a correlation of inhibitory power to insecticidal activity.     

Enhancement of neurotransmitter release from invertebrate synaptosomes by pyrethroids during pulsed-depolarization: A functional assay for effects on repolarization

The release of [³H]neurotransmitters was used as a functional assay to assess the actions of selected neurotoxins on the synaptosomal membranes prepared from the invertebrate nervous systems of squid and house fly. A reproducible release of [³]neurotransmitter was evoked by pulsed-depolarization in the presence of elevated K⁺ or of veratridine. Pretreatment with deltamethrin resulted in a substantial enhancement of [³H]neuro-transmitter release during pulsed-depolarization. This enhanced neurotransmitter release was greatly reduced or absent when synaptosomes of knockdown-resistant house flies were examined. No enhanced neurotransmitter release due to deltamethrin pretreatment was apparent from any synaptosomal preparation under non-depolarizing conditions. Under similar conditions, collaborative experiments demonstrated that deltamethrin causes a significant change in protein phosphorylation activities which follow depolarization. The most significant change caused by deltamethrin was the prolonged elevation of the level of phosphorylation on a number of key synaptic proteins beyond the normal time of their recovery to the dephosphorylated state. The most notable protein reacting to deltamethrin in this manner was calcium-cadlmodulin-dependent protein kinase.     

Pyrethroid insecticides: Potent,stereospecific enhancers of mouse brain sodium channel activation

Deltamethrin and NRDC 157, pyrethroid insecticides that produce different poisoning syndromes in mammals, enhanced veratridine-dependent, sodium channel-mediated ²²Na⁺ uptake in mouse brain synaptosomes. Concentrations producing half-maximal enhancement were 2.5 × 10^?8M (deltamethrin) and 2.2 × 10^?7M (NRDC 157). This effect was stereospecific: The nontoxic 1S enantiomers had no significant effect on veratridine-dependent activation. At high deltamethrin concentrations, enhancement was maximal at 5 × 10^?5?1 × 10^?4M veratridine. Pyrethroid enhancement was completely blocked by 5 × 10^?6M tetrodotoxin, and neither pyrethroid affected ²²Na⁺ uptake in the absence of veratridine at concentrations up to 1 × 10^?5M. The relative potencies of deltamethrin and NRDC 157 in the synaptosomal sodium channel assay agree well with their relative acute toxicities to mice when administered by intracerebral injection. These findings demonstrate that pyrethroids exemplifying both characteristic poisoning syndromes are potent, stereospecific modifiers of sodium channel function in mammalian brain.     

PKC-dependent phosphorylations modify the action of deltamethrin on rat brain N-type (CaV2.2) voltage-sensitive calcium channel

Voltage clamp electrophysiological studies using wild type Ca_V2.2 and its β₃ subunit coexpressed in Xenopus oocytes revealed that deltamethrin increased the rate of activation, prolonged inactivation and reduced peak current. Site-directed mutagenesis of threonine 422 to glutamic acid (T422E, one of five protein kinase C (PKC)-dependent phosphorylation sites) resulted in a channel that acted as if it were permanently phosphorylated. This resulted in an increased probability of opening during depolarization and a reduced inhibition by the βγ subunit of heterotrimeric G-protein. Deltamethrin treatment of T422E Ca_V2.2 enhanced peak current ∼50% over ethanol-treated controls with an EC₅₀ of 9.8 × 10⁻¹¹ M.Phosphorylation of wild type Ca_V2.2 is evoked by the phorbol ester, phorbol 12-myristrate, 13 acetate (PMA), by activating endogenous protein kinase C (PKC) in oocytes. PKC-dependent phosphorylation activated by PMA of wild type Ca_V2.2 has been previously shown to slow channel deactivation and increased Ca²⁺ influx and subsequent neurotransmitter release. Following PMA-activated phosphorylation, deltamethrin significantly increased peak current and slowed deactivation of the phosphorylated channel, which would be consistent with slower channel closure, greater Ca²⁺ influx and enhanced neurotransmitter release seen in vivo. Deltamethrin treatment in the absence of PMA-activated phosphorylation resulted in no effect on the deactivation kinetics of unphosphorylated Ca_V2.2 or the T422E mutant. Thus, Ca_V2.2 is modified by deltamethrin but the resulting perturbations are dependent upon its PKC-dependent phosphorylation state.     

Evidence of synergy between prochloraz and deltamethrin in apis mellifera L.: a convenient biological approach

We have studied the synergistic action of deltamethrin and prochloraz in bees in laboratory experiments that allowed us to express dosages in terms of field rates (g ha^?1). It was established that, used alone, deltamethrin at 0·125 g ha^?1 and prochloraz at 25 g ha^?1 did not produce mortalities different from that of the control during 96 h of observation. Sprayed as a mixture of these doses, deltamethrin and prochloraz produced 67·5% corrected mortality within 24 h and 74·1% corrected mortality within 50 h. Sequential treatments of deltamethrin and prochloraz spaced by a 0·8-day interval reduced the synergistic action of both molecules. At 50 h, the lethal effects were 27·5% corrected mortality for the treatment of deltamethrin followed by prochloraz and 23·8% corrected mortality for the treatment of prochloraz followed by deltamethrin. Results are discussed in terms of mode of action and sub-lethal effects.     

Effects of deltamethrin on ventral nerve cord activity in the cockroach

The effects of varying concentrations of deltamethrin on a number of the parameters of electrophysiological activity in the cockroach ventral nerve cord have been studied. Deltamethrin, at concentrations greater than 100 nM, caused repetitive firing in the central nervous system (CNS), prior to conduction block, the effect getting faster as the concentration was increased. Whilst 10-nM deltamethrin eventually caused conduction block with no apparent increase in the level of CNS activity, it induced a gradual decrease in the amplitudes of all spike activity. Deltamethrin at 10μM induced a significant increase in the latency of electrically evoked responses, and this was attributed to a synaptic mechanism. It was shown for the first time that 10-μM deltamethrin causes a significant elevation of the extra-axonal K⁺ activity; the possible consequences of this are discussed.     

Is sulfotep a proctolin receptor antagonist?

Proctolin-induced, dose-dependent (10^?8-2 × 10^?6 M) contraction of the isolated foregut of Schistocerca gregaria was antagonised non-competitively by sulfotep (2 × 10^?6-10^?5 M). A higher dose of sulfotep (5 × 10^?5 M) caused restoration of the proctolin dose-response curve to its control value. Neostigmine (10^?5 M) caused non-competitive inhibition of proctolininduced tissue contraction. Increasing the dose of neostigmine to 10^?4 M restored the proctolin response to control values. Sulfotep (10^?5 M) and neostigmine (10^?4 M) caused inhibition of acetylcholinesterase (AChE) activity in tissue homogenates obtained from guts pretreated with either drug for 20 min. The stimulatory effect of sulfotep (5 × 10^?5 M) on proctolin-induced gut contraction was abolished by pretreatment of tissues with atropine (10^?6 M). Under these conditions, 5 × 10^?5 M sulfotep caused further antagonism of the action of proctolin. The results suggest that sulfotep is a proctolin receptor antagonist in the locust foregut. However, higher concentrations inhibit tissue AChE activity, thereby allowing endogenous acetylcholine to activate muscarinic receptors. This leads to enhanced tissue contractility which masks the antagonistic effect of sulfotep on proctolin-induced contraction.     

Sulfur in pesticide action and metabolism: Edited by J. D. Rosen,P. S. Magee,and J. E. Casida,American Chemical Society,Washington, D.C., 1981. 172 pp., $33.00

The distribution of ¹⁴C-acid-, ¹⁴C-alcohol-, and ¹⁴C-cyano-labeled deltamethrin and selected metabolites were followed in the liver, blood, cerebrum, cerebellum, and spinal cord after iv administration of a toxic, but nonlethal dose (1.75 mg/kg) to rats. Approximately 50% of the dose was cleared from the blood within 0.7–0.8 min, after which the rate of clearance decreased. 3-Phenoxybenzoic acid (PBacid) was isolated from the blood in vivo, and was also the major metabolite when ¹⁴C-alcohol-labeled deltamethrin was incubated with blood in vitro. Deltamethrin levels in the liver peaked at 7–10 nmol/g at 5 min and then decreased to 1 nmol/g by 30 min. In contrast, peak central nervous system levels of deltamethrin were achieved within 1 min (0.5 nmol/g), decreasing to 0.2 nmol/g at 15 min, and remaining stable until 60 min. peak levels of deltamethrin did not correspond to the severity of toxicity, although the levels of non-pentane-soluble radiolabel did appear to correlate with motor signs of toxicity. Experiments with brain homogenates, using in vivo concentrations of deltamethrin, failed to reproduce the pentane-unextractable radioactivity in vitro nor was any metabolism demonstrated.     

Toxico‐kinetics,recovery efficiency and microsomal changes following administration of deltamethrin to black Bengal goats

A study of the toxico‐kinetics, recovery percentage from different substrates, cytotoxicity and role of cytochrome P₄₅₀ and b₅ of liver microsome in the metabolism of deltamethrin were carried out in female black Bengal goat. The ALD₅₀ value of deltamethrin in goat by intravenous route lies between 0.2 and 0.6 mg kg^?1. Intravenous disposition kinetics using a dose of 0.2 mg kg^?1 showed that the maximum blood concentration of deltamethrin was recorded at 0.5 min, followed by rapid decline, and a minimum concentration was detected at 6 min after administration. The following values were obtained : Vd_area 0.148 (± 0.02) litre kg^?1; t_1/2 (α) 0.22 (± 0.02) min; t_1/2 (β) 2.17 (± 0.37) min; K_el 1.05 (± 0.24) min^?1; AUC 4.30(± 0.45) µg min ml^?1; Cl_B 0.05 (± 0.006) litre kg^?1 min^?1; T～B 1.93 (± 0.58); fc 0.40(± 0.05). After 10 min, liver retained the maximum residue, and heart, adrenal gland, kidney, spleen, fat and brain also held the insecticide; liver, fat, heart and spleen retained residue after 30 min, and bone, liver and fat retained residue after 60 min of intravenous administration. Oral absorption of deltamethrin was poor and inconsistent, and approximately 65% of administered dose was recovered from faeces and gastrointestinal contents. The excretion of deltamethrin through urine was meagre, and only 0.01 and 0.013% of the administered dose was recovered after 3 and 5 days of oral administration respectively. All the tissues retained the residue after 3 days; while fat, rumen, reticulum, omasum, abomasum, large and small intestine and bone retained the residue after 5 days of oral administration; and the percentage recoveries were 1.73 and 0.027 respectively. Deltamethrin reduced the level of cytochrome P₄₅₀ content of liver microsomal pellet of goat after 5 days of oral administration. Histopathological examination of liver, kidney, heart, spleen brain and lung sections of treated goats did not reveal any pathological changes. © 2001 Society of Chemical Industry     

Cholinergic properties of pinched-off synaptic nerve endings from the central nervous system of the cockroach Periplaneta americana

The preparation and cholinergic properties of a subcellular fraction, enriched in pinched-off nerve-endings (synaptosomes) from the central nervous system of the cockroach Periplaneta americana, are described. The endings retained their cytoplasmic components, as shown by the presence of marker enzymes and by ultrastructural examination. A carrier-mediated, high-affinity uptake of [³H] choline into the synaptosomes was demonstrated, and this uptake was saturable, depended on a Na⁺-gradient, and was inhibited by hemicholinium-3. It had an apparent K_m value of 0.6 (±0.1) μM, and a V_max of 20.5 (±2.5) pmol min^?1 per mg of protein. The high-affinity [³H]choline uptake was associated with the synthesis of [³H]phosphocholine and [³H]O-acetylcholine. The rate of [³H]choline uptake in synaptosomes was increased by DDT [1,1,1-trichloro-2,2-bis(4-chlorophenyl) ethane] at 100 nM concentration, and this increase was inhibited by tetrodotoxin, while neostigmine appeared to be a potent inhibitor (I₅₀ = 10 pM) of the DDT-activated uptake of [³H]choline. The site of action of the insecticides was specifically on the pre-synaptic nerve terminals because the synaptosomes preparation did not retain the post-synaptic membrane of the original nerve-endings. Cockroach synaptosomes provided a useful in-vitro preparation for studying the effects of insecticides on the pre-synaptic nerve endings.     

Effect of CGA 123407 as a safener for pretilachlor in rice (Oryza sativa L.). Recordings of elongation rates of single rice leaves

The elongation rates of single attached leaves of rice (Oryza saliva L.) were recorded. The effect of pretilachlor on the elongation rates and the safening effect of CGA 123407 [4, 6-dichloro-2-phenyl-pyrimidine] were evaluated. Both chemicals were applied to the roots in a nutrient solution. Pretilachlor reduced leaf elongation in concentrations as low as 300 μg^?1 (9–6 × 10^?7 M) but. for combination trials with the safener, 3 mg 1^?1 (9–6 × 10^?6 M) was used. in combination with pretilachlor the safener prevented damage in very low concentrations. The ratio of pretilachlor to safener, 30:1, was sufficient when both chemicals were given to roots in nutrient solution, although for field work the ratio of 3:1 is recommended. The safener alone did not influence the elongation rate of rice leaves in the concentrations used. When pretilachlor was given to the roots and CGA 123407 to the shoot, some delay in the herbicidal action was recorded but even with high concentrations of the safener no continuous safening effect was achieved. CGA 123407 was also effective when given previous to the herbicide. This proved true even with a 2-day interval between safener uptake and application of the herbicide. When pretilachlor was given first, the safener effected recovery to various degrees when given 1–4 days after the herbicide application. When pretilachlor was given for a limited period of time only (1–3 days) and was subsequently removed from the nutrient solution, recovery of the plant occurred. It is speculated that the safener either helps this recovery or else competitively prevents the herbicide from occupying the sites of action or from keeping them occupied for a long period of time.     

Binary mixtures of pyrethroids produce differential effects on Ca influx and glutamate release at isolated presynaptic nerve terminals from rat brain

Isolated rat brain synaptosomes were used to evaluate the action of pyrethroid mixtures on Ca²⁺ influx and subsequent glutamate release under depolarizing conditions. In equipotent binary mixtures at their respective and/or estimated EC₅₀s with deltamethrin always as one of the two components, cismethrin, λ-cyhalothrin, cypermethrin, esfenvalerate and permethrin were additive and S-bioallethrin, fenpropathrin and tefluthrin were less-than-additive on Ca²⁺ influx. In binary mixtures with deltamethrin always as one of the two components, esfenvalerate, permethrin and tefluthrin were additive and λ-cyhalothrin was less-than-additive on glutamate release. Binary mixture of S-bioallethrin and cismethrin was additive for both Ca²⁺ influx and glutamate release. Only a subset of pyrethroids (S-bioallethrin, cismethrin, cypermethrin, and fenpropathrin) in binary mixtures with deltamethrin caused a more-than-additive effect on glutamate release. These binary mixtures were, however, only additive (cismethrin and cypermethrin) or less-than-additive (S-bioallethrin and fenpropathrin) on Ca²⁺ influx. Therefore, increased glutamate release evoked by this subset of pyrethroids in binary mixture with deltamethrin is not entirely occurring by Ca²⁺-dependent mechanisms via their action at voltage-sensitive calcium channels. These results suggest that pyrethroids do not share a common mode of toxicity at presynaptic nerve terminals from rat brain and appear to affect multiple target sites, including voltage-sensitive calcium, chloride and sodium channels.     

CNS insensitivity to pyrethroids in the resistant kdr strain of house flies

Solutions of tetramethrin, RU 11679, or cismethrin caused uncoupled convulsions in 30–40 min in exposed thoracic ganglia from S_NAIDM house flies at concentrations down to 10^?10M: whereas these same compounds at 10^?6M concentrations failed to produce poisoning symptoms when perfused onto the exposed ganglia of the kdr strain of house fly. The pyrethroid analogs examined had a negative temperature coefficient of action on the exposed thoracic ganglia from S_NAIDM flies. DDT and GH-74 possessed positive temperature coefficients of action on the exposed thoracic ganglion of susceptible house flies. It is concluded that the central nervous system of the kdr strain of house fly is resistant to pyrethroid action; furthermore, the resistance appears to be widespread throughout the house fly nervous system, involving sensory, motor, and central neural elements.     

Mutation of threonine 422 to glutamic acid mimics the phosphorylation state and alters the action of deltamethrin on Cav2.2

Effects of deltamethrin on voltage-sensitive calcium channels (VSCC) from rat brain (Ca_v2.2) expressed in Xenopus oocytes were assessed electrophysiologically. Deltamethrin reduced peak current of wild-type Ca_v2.2 in a stereospecific and concentration-dependent manner with an EC₅₀ of 1 × 10⁻⁹ M. Phosphorylation of threonine 422 enhances voltage-sensitive calcium current, increases the probability that Ca_v2.2 will open under depolarizing conditions and antagonizes the inhibition of the channel by the betagamma subunit of heterotrimeric G-protein (Gβγ). Site-directed mutagenesis of threonine 422 to glutamic acid (T422E) results in a channel that acts as if it were permanently phosphorylated. Deltamethrin (10⁻⁷ M) significantly enhanced peak current via the T422E channel (1.5-fold) compared to the nontreated control and the increase was significantly greater than for either the wild-type (T422) or T422A (permanently unphosphorylated mutant) channels. The effect of deltamethrin on T422E Ca_v2.2 was stereospecific and concentration-dependent with an EC₅₀ of 9.8 × 10⁻¹¹ M. Thus, Ca_v2.2 is modified by deltamethrin but the resulting perturbation is dependent upon the phosphorylation state of threonine 422.     

Electrophysiological identification of site-insensitive mechanisms in knockdown-resistant strains (kdr,super-kdr) of the housefly larva (Musca domestica)

The effects of pyrethroids were studied upon isolated segmental nerves and neuromuscular junctions in both susceptible (Cooper) and knockdown-resistant (kdr; super-kdr) strains of housefly larvae (Musca domestica L.). Isolated segmental nerves contained neither cell bodies nor synaptic contacts; thus, any effects of pyrethroids were attributed solely to their actions upon voltage-dependent Na⁺ channels. Threshold concentrations of the type II pyrethroid, deltamethrin, required to elevate the spontaneous firing rate of these nerves were determined. Both resistant strains were about ten times less sensitive to deltamethrin than the susceptible strain, but insensitivity of super-kdr nerves was no greater than in the less resistant kdr strain. At neuromuscular junctions, the minimum concentrations of pyrethroids needed to trigger massive increases in the frequency of miniature excitatory postsynaptic potentials (mEPSPs) were determined for deltamethrin and the type I pyrethroid, fenfluthrin. With fenfluthrin there was no detectable difference between the junctions of kdr and super-kdr strains, which were both about ten-fold less sensitive than Cooper junctions. With deltamethrin, kdr junctions were about 30 times less sensitive than those of Cooper; super-kdr junctions were dramatically insensitive to deltamethrin, being some 10000- and 300-fold less sensitive than those of Cooper and kdr respectively. Thus, in the synaptic assay, super-kdr conferred an extension in resistance over kdr only against the type II pyrethroid, it being ineffective against fenfluthrin. We suggest that kdr resistance comprises at least two site-insensitive areas within the nervous system. One involves insensitivity of the Na⁺ channel and has similar efficacy in both kdr and super-kdr strains against type I and II pyrethroids; the other is associated with the presynaptic terminal and is particularly effective in super-kdr resistance against type II pyrethroids. The latter could be associated with Ca²⁺-activated phosphorylation of proteins involved with neurotransmitter release. Such phosphorylation reactions are known to be perturbed by pyrethroids, especially by type II compounds.     

Action of avermectin B1a on the leg muscles and the nervous system of the American cockroach

The action of avermectin was studied in the leg muscle and the central nervous system of the American cockroach, Periplanata americana L. Avermectin at a low concentration (10^?7M) causes a failure of the leg muscles to respond to external stimuli within 30 min without affecting the magnitude of contraction. Avermectin was found to stimulate Cl^? uptake by the leg muscles within 4 min at 10^?7M. The threshold concentration to cause such stimulation was on the order of 10^?8M. This stimulatory action could be antagonized by picrotoxinin (10^?4M) and to a lesser extent by bicuculline methiodide (10^?4M). The phenomenon is observable under both Na⁺-free and K⁺-free conditions. It was concluded that the action of avermectin is to open the chloride channel on the plasma membrane. This action of avermectin does not seem to be mediated through GABA, GABA receptors, diazepine receptors, or picrotoxinin receptor in this insect species, and therefore suggests that avermectin directly attacks the chloride channel proper both in the central nervous and the neuromuscular systems.     

Neurotoxic implications of the agonistic action of CS-syndrome pyrethroids on the N-type Ca(v)2.2 calcium channel

BACKGROUND: Cismethrin (T-syndrome) and deltamethrin (CS-syndrome) pyrethroids have been previously shown to increase membrane depolarization and calcium influx, but only deltamethrin increased Ca(2+)-dependent neurotransmitter release from rat brain synaptosomes. Deltamethrin's action was blocked by omega-conotoxin GVIA, delineating a separate action at N-type Ca(v)2.2 channels that is consistent with the in vivo release of neurotransmitter. It is hypothesized that other CS-syndrome pyrethroids will elicit similar actions at presynaptic nerve terminals.RESULTS: Nine additional pyrethroids were similarly examined, and these data were used in a cluster analysis. CS-syndrome pyrethroids that possessed alpha-cyano groups, cypermethrin, deltamethrin and esfenvalerate, all caused Ca(2+) influx and neurotransmitter release and clustered with two other alpha-cyano pyrethroids, cyfluthrin and cyhalothrin, that shared these same actions. T-syndrome pyrethroids, bioallethrin, cismethrin and fenpropathrin, did not share these actions and clustered with two non-alpha-cyano pyrethroids, tefluthin and bifenthrin, which likewise did not elicit these actions. Deltamethrin reduced peak current of heterologously expressed wild-type Ca(v)2.2, increased peak current of T422E Ca(v)2.2 and was 20-fold more potent on T422E Ca(v)2.2 than on wild-type channels, indicating that the permanently phosphorylated form of Ca(v)2.2 is the preferred target.CONCLUSIONS: Ca(v)2.2 is directly modified by deltamethrin, but the resulting perturbation is dependent upon its phosphorylation state. The present findings may provide a partial explanation for the different toxic syndromes produced by these structurally distinct pyrethroids.     

Comparative effects of organophosphorus insecticides on the activities of acetylcholinesterase,diacylglycerol kinase,and phosphatidylinositol phosphodiesterase in rat brain microsomes

The activities of acetylcholinesterase, diacylglycerol kinase, and phosphatidylinositol phosphodiesterase in rat brain microsomes were measured in the presence and absence of the organophosphorus insecticides, parathion and diazinon, and their respective oxon analogs, paraoxon and diazoxon. Marked inhibition of acetylcholinesterase (by 45–99%) was observed in the presence of paraoxon (10^?2–10^?6M) and diazoxon (10^?2–10^?4M). Reduction of acetylcholinesterase activity (by 22–33%) was achieved with the parent insecticides at high concentrations only (10^?2M). In most cases, diacylglycerol kinase was insensitive to the pesticides. Marked stimulation of phosphatidylinositol phosphodiesterase (by 10–57%) was observed in the presence of all pesticides (10^?2–10^?3M). The phosphodiesterase exhibited slightly greater sensitivity to the parent compounds compared to the oxon derivatives. Stimulation of the phosphodiesterase by the insecticides was not correlated with acetylcholinesterase inhibition. Accordingly, the increase in phosphodiesterase activity was judged not to be acetylcholine mediated, but rather represented a direct effect of the pesticides on the enzyme or its microenvironment. Based on the present in vitro observations, it is proposed that certain organophosphorus pesticides may interfere with the normal process of synaptic transmission through both the inhibition of acetylcholinesterase and the stimulation of phosphatidylinositol phosphodiesterase. In view of the high concentrations of pesticides required to elicit the latter effect, interpretation of its physiological significance must await results from further studies performed in vivo.     

Fate and persistence of residues on wheat used to explain efficacy differences between deltamethrin suspension concentrate and emulsifiable concentrate formulations

To help explain the increased residual activity of a deltamethrin suspension concentrate (SC) formulation against grasshoppers, the persistence, location and nature of residues from the SC and an emulsifiable concentrate (EC) formulation have been compared. Wheat plants were sprayed in a cabinet sprayer at 7.6 g ha^?1 for the EC and 5.6 g ha^?1 for the SC, then weathered outdoors for 16 days. With the SC formulation, residues were more persistent, more residues were located on the exterior of the leaves, and less deltamethrin was converted to inactive isomers. Eight days after spraying, the exterior deltamethrin residues were 0.13 μg plant^?1 from the SC versus 0.06 μg plant^?1 from the EC. Thus, more residual deltamethrin is available to grasshoppers with the SC formulation.