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.     

Action of pyrethroids on a nerve-muscle preparation of the clawed frog,Xenopus laevis

The effects of a range of pyrethroids on end-plate potentials and muscle action potentials were studied in the pectoralis nerve-muscle preparation of the clawed frog, Xenopus laevis. The noncyano pyrethroids allethrin, cismethrin, bioresmethrin, and IR-cisphenothrin caused moderate presynaptic repetitive activity only, resulting in the occurrence of multiple end-plate potentials (epps). Trains of repetitive muscle action potentials without presynaptic repetitive activity were observed after the α-ethynyl pyrethroid S-5655 and after the α-cyano pyrethroids cypermethrin, deltamethrin, FCR 1272, and FCR 2769. An intermediate group of pyrethroids consisting of the non-cyano compounds 1R-permethrin, des-cyano-deltamethrin, NAK 1901 and NAK 1963, and the α-cyano pyrethroids cyphenothrin and fenvalerate caused both types of effect. The insecticidally inactive S-enantiomers of permethrin had no effect on the nerve-muscle preparation. Trains of repetitive action potentials in pyrethroid-treated muscle fibers were followed by a depolarizing afterpotential which in general decayed more rapidly for the non-cyano pyrethroids than for the α-cyano pyrethroids. The rate of decay of the depolarizing afterpotential decreased gradually as the temperature was lowered, whereas the pre- and postsynaptic repetitive activity remained largely unaffected over a large temperature range. It is concluded that in muscle membrane like in nerve membrane the pyrethroid-induced repetitive activity is due to a prolongation of the sodium current and that a clear distinction between non-cyano pyrethroids on the one hand and α-cyano compounds on the other cannot be made on the basis of the present results.     

Promotion of norepinephrine release and inhibition of calcium uptake by pyrethroids in rat brain synaptosomes

A series of 25 pyrethroids were assessed for their effects on Na⁺-dependent norepinephrine release and on Ca²⁺ uptake in vitro using a crude rat brain synaptosomal preparation. The most effective pyrethroids required a concentration of 3–10 μM to promote norepinephrine release. Plotting release data versus lipophilicity (as log P) for each compound resulted in a parabolic curve with log P_opt being 5.4 for maximal release. The release promoted by most of the compounds assessed at 30 μM could not be or was only partially reversed by either tetrodotoxin or substituting choline for Na⁺ conditions which readily reversed the release promoting effects of veratridine. Thus, many pyrethroids, particularly those without the α-cyano group, did not display their expected effects on the Na⁺ channel in rat brain. When assessed at 5 μM, pyrethroids inhibited, had no effect, or caused increases in the amount of Ca²⁺ incorporated in the presence of ATP. The effectiveness of the various pyrethroids to inhibit Ca²⁺ uptake again displayed a parabolic relationship with log P_opt being 6.4. It was concluded that the variations in pyrethroid effects on norepinephrine release and Ca²⁺ uptake are not solely related to their particular chemical structures, but to lipophilicity. The effects of many pyrethroids on Ca²⁺ metabolism, particularly displacement of bound Ca²⁺, better explain the transmitter release promoting properties in vitro rather than a direct effect on the Na⁺ channel. No direct relationship between known toxicity to mammals and Ca²⁺ inhibition by pyrethroids was established.     

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.     

Pyrethroid toxicology: Mouse intracerebral structure-toxicity relationships

Mouse intracerebral (ic) toxicity studies with 29 pyrethroids confirm earlier mouse intraperitoneal (ip) and rat oral and intravenous findings in three respects: α-cyano-3-phenoxybenzyl esters produce choreoathetosis, convulsions, and salivation, whereas compounds lacking the α-cyano group yield tremors and convulsions; high stereospecificity is involved in inducing both poisoning syndromes; large toxicity differences for (1R,trans) vs (1R,cis) resmethrin and permethrin do not extend to ethanomethrin and the cyanophenoxybenzyl esters. The ic investigations further establish that: profuse salivation is not unique for pyrethroids with the α-cyano group; the inactivity of (1R,trans) resmethrin in the brain is not due to detoxification; pyrethroids acting most rapidly in the brain are those with the highest knockdown activity for insects; the cyanophenoxybenzyl esters, in comparison with the non-cyano pyrethroids, have a high ic toxicity relative to their synergized ip toxicity indicating the importance of the brain in the Type II poisoning syndrome.     

Structure-related effects of pyrethroid insecticides on the lateral-line sense organ and on peripheral nerves of the clawed frog, Xenopus laevis

The effects of seven different pyrethroid insecticides on the lateral-line sense organ and on peripheral nerves of the clawed frog, Xenopus laevis, were investigated by means of electrophysiological methods. The results show that two classes of pyrethroid can be clearly distinguished. (i) Pyrethroids without an α-cyano group (permethrin, cismethrin, and bioresmethrin). These noncyano pyrethroids induce short trains of nerve impulses in the lateral-line sense organ. In peripheral nerve branches they induce a depolarizing afterpotential and repetitive firing. These effects are very similar to those previously reported for allethrin. (ii) Pyrethroids with an α-cyano-3-phenoxybenzyl alcohol (cypermethrin, fenpropathrin, deltamethrin, and fenvalerate). In the lateral-line sense organ these α-cyano pyrethroids induce very long trains of nerve impulses which may last for seconds and may contain hundreds or even thousands of impulses. The α-cyano compounds do not cause repetitive activity in peripheral nerves. Instead they induce a quickly reversible, stimulus frequency-dependent suppression of the action potential. Since the chemical structure of cypermethrin differs from that of permethrin only in the α-cyano group and because all four α-cyano compounds act in a very similar way, it is concluded that the α-cyano substituent is responsible for the large differences in neurotoxic effects. In the lateral-line sense organ the duration of nerve impulse trains induced by the noncyano as well as the α-cyano pyrethroids increases dramatically when the temperature is lowered. Further, in sensory fibers the effects of both classes of pyrethroid on the nerve action potential are more pronounced compared to their effects on motor fibers. It is argued that the different neurotoxic effects reported here originate from a common mechanism of action of pyrethroids, which is a prolongation of the transient increase of sodium permeability of the nerve membrane associated with excitation.It is concluded that the sodium channel in the nerve membrane is the major target site of noncyano and α-cyano pyrethroids.     

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 N-type (Cav2.2) voltage-sensitive calcium channels in rat brain

Isolated presynaptic nerve terminals prepared from whole rat brain were used to evaluate the action of deltamethrin on voltage-sensitive calcium channels by measuring calcium influx and endogenous glutamate release. Deltamethrin-enhanced K⁺-stimulated calcium influx and subsequent Ca²⁺-dependent glutamate release. The effect of deltamethrin was concentration-dependent, stereospecific, blocked by ω-conotoxin MVIIC but unaltered in the presence of tetrodotoxin. These results suggest that N-type voltage-sensitive calcium channels are a site of action at the presynaptic nerve terminal. Electrophysiological studies were carried out using rat brain Ca_v2.2 and β₃ subunits coexpressed in Xenopus oocytes to validate such action. Deltamethrin reduced barium peak current in a concentraion-dependent and stereospecific manner, increased the rate of activation, and prolonged the inactivation rate of this channel. These experiments support the conclusion that N-type voltage-sensitive calcium channel operation is altered by deltamethrin.     

Deltamethrin: A neurophysiological study of the sites of action

Recent experiments on the mode of action of pyrethroids have indicated that those pyrethroids containing an α-cyano phenoxybenzyl group may act on GABA-mediated chloride channels. The crayfish stretch receptor neuron provides a useful preparation for examining the effects of pyrethroids on these channels and on sodium channels. The lowest concentration of deltamethrin to have an effect on sodium channels was 10⁻¹² M, but the response of the preparation to GABA appeared to be unaffected by concentrations of deltamethrin up to 10⁻⁷ M. Although 10⁻⁶ M deltamethrin had a slight effect on the GABA response of the dactyl abductor muscle, it appears that the majority of the effects of cyano pyrethroids in invertebrates could be accounted for solely by their action on sodium channels.     

Quantitative structure-activity studies of substituted benzyl chrysanthemates: 9. Calcium uptake inhibition in crayfish nerve cord and lobster axon homogenates in vitro by sunthetic pyrethroids

Twenty-five synthetic pyrethroids and related chemicals were assessed for their effects on the uptake of Ca²⁺ (as ⁴⁵Ca²⁺) by crude homogenates prepared from crayfish (Procambarus clarkii) nerve cords and 20 were assessed on the uptake by homogenates prepared from lobster (Panulirus japonicus) axons. A parabolic relationship was demonstrated between inhibition of Ca²⁺ uptake for this series of chemicals and lipophilicity (log P) in both species when tested at 5 μM. Optimal log P for maximal inhibition was located at about 6.6 and 84(±6)% inhibition was obtained with resmethrin. Compounds of higher or lower log P were either weaker inhibitors, not inhibitors or occasionally resulted in slightly increased levels of Ca²⁺ uptake. No direct correlations between the potential for the pyrethroids to inhibit Ca²⁺ uptake and the potential for these agents to increase the frequency of spontaneous discharges in crayfish nerve cords, to induce repetitive firing in American cockroaches, or the lethality to cockroaches or to any other neurophysiological or toxicity parameter could be established. It was concluded that although some synthetic pyrethroids are moderately potent inhibitors of Ca²⁺ uptake into nerve cord and axonic preparations (i.e., I₅₀ for trans-resmethrin equals 1 μM) this inhibition alone does not relate to the neurophysiological changes in isolated nerve preparations or to the toxicity of these agents in insects.     

The crayfish stretch receptor organ: A useful model system for investigating the effects of neuroactive substances: I. The effect of DDT and pyrethroids

The crayfish stretch receptor organ is a useful model system for investigating the effects of neuroactive compounds on an invertebrate sensory cell. The receptor neuron is very sensitive to pyrethroids, DDT, and veratridine, and comparisons were made between the effects of α-cyano substituted pyrethroids (cypermethrin and deltamethrin) and pyrethroids without a cyano group (permethrin and bioallethrin). A comparison of the effects of pyrethroids on this single sensory cell with those recorded from the flight muscles of a whole insect (Lucilia sericata) indicates that the effects are similar in both preparations.     

Inhibition by decamethrin and resmethrin of hormone release from the isolated rat neurohypophysis—A model mammalian neurosecretory system

The isolated rat neurophypophysis, which shows a calcium-dependent hormone release when depolarized in vitro was used as a model system to investigate the effects of the pyrethroids decamethrin and resmethrin on mammalian nervous tissue. Both compounds inhibited neurohypophysial hormone release in response to electrical stimulation, decamethrin being more potent than resmethrin. Decamethrin reduced the hormone content of the neurohypophysis. Resmethrin did not reduce stored hormone significantly and its effects on release were dose dependent. They could be mimicked by raising the [Na⁺] of the medium but not by lowering the [Ca²⁺]. Resmethrin had no effect on the release of hormone following depolarization of the tissue with a raised [K⁺]. The results are consistent with the suggestion that the compounds do not act on the potential-dependent secretion process but rather on the mechanism linking depolarization of the secretory terminals with the arrival of action potentials possibly by interfering with sodium-channel activation and inactivation.     

Two different types of inhibitory effects of pyrethroids on nerve Ca- and Ca + Mg-ATPase activity in the squid, Loligo pealei

The biochemical process by which various pyrethroid insecticides affect membrane-bound ATPase activities of the squid nervous system was examined. Of the five ATP-hydrolyzing systems tested, only Ca²⁺-stimulated ATPase activities are seen to be clearly affected by pyrethroids. It was found that the “natural type” pyrethroids (e.g., pyrethrin and allethrin) primarily inhibit Ca-ATPase activity whereas the “highly modified type” pyrethroids (e.g., cypermethrin and decamethrin) mainly inhibit Ca + Mg-ATPase. permethrin, which is considered to possess structural similarities to both the natural type and the highly modified type pyrethroids, was found to have an intermediate property in terms of its inhibitory potency to both Ca- and Ca + Mg-ATPase activities. The level of inhibition of Ca²⁺-stimulated ATPase activities was generally high in the retinal axons and optic lobe synaptosomes but lowest in the axoplasmic preparations.     

Alterations of offspring heart muscle electrical activity transferred by rat male genitors chronically treated with lindane (γ-hexachlorocyclohexane) trace concentrations

Using intracellular microelectrodes, we studied transmembrane resting and action potentials (AP) of left ventricle papillary muscles isolated from the heart of adult lindane-treated (TMG) and untreated (UMG) male genitor rat offspring, obtained by mating untreated female with males chronically treated and untreated with lindane (2 ppb) trace concentrations through beverage. The AP magnitude and duration (APD) were similar in both groups and their response to low temperature (22 °C) unchanged. Lowering the external Ca²⁺ concentration from 2.5 to 0.625 mM prolonged APD in the TMG group but not in the UMG group. In the TMG group, (i) cumulative addition of Sr²⁺ (1 mM) to the physiological solution prolonged APD; (ii) apamin (4 μM) and charybdotoxin (4 μM) prolonged the APD. In conclusion, our data revealed that an altered sensitivity of the Ca²⁺-induced Ca²⁺ inactivation of L-type Ca²⁺ channels and of Ca²⁺-activated K⁺ channels to Ca²⁺ has been transferred to TMG offspring.     

Depolarization of motor nerve terminals by pyrethroids in susceptible and kdr-resistant house flies

When applied at concentrations of one nM or higher to a house fly larval neuromuscular preparation, deltamethrin (DM) and fenvalerate (FV) greatly increased miniature excitatory postsynaptic potential (mepsp) rate and blocked neuromuscular transmission. The DM-induced mepsp discharge was abolished by tetrodotoxin (TTX), removal of Ca²⁺ from the saline, or by application of hyperpolarizing stimuli to the nerve, indicating that it was due to depolarization of the presynaptic terminals. Also, in the presence of TTX, K⁺ depolarization increased mepsp rate at the same external K⁺ concentration before and after DM treatment, confirming that DM released transmitter by depolarizing the nerve terminals rather than by altering the voltage dependence of transmitter release. The potassium channel blocker tetraethylammonium (TEA) increased mepsp rate somewhat, while aconitine (20 μM), which keeps sodium channels open, increased mepsp rate consistently. Pretreatment of nerves with a subthreshold dose of TEA greatly increased the mepsp rate-increasing activity of DM and aconitine, while a subthreshold level of aconitine did not synergize DM. These observations suggest that DM, like aconitine, depolarized nerves by modifying the sodium channels. Knockdown resistant (kdr) larvae were resistant to the depolarizing action of DM and aconitine but not to that of TEA, indicating that the kdr gene produced a modified sodium channel which was less sensitive to the action of pyrethroids and aconitine. During sustained transmitter release by DM, evoked release gradually declined, resulting in a condition called early block in which spontaneous release was high and release could be evoked by electrotonic depolarization of the nerve terminals, but not by a nerve action potential. Early block was probably due to conduction block in the nerve terminals. Early block eventually gave way to late block, characterized by the decline of spontaneous release to subnormal levels and complete failure of evoked release. After late block, the calcium ionophore X-537A could not release transmitter, suggesting that late block was due to depletion of available transmitter. DM did not have a direct effect upon extrasynaptic muscle membrane. However, after late block, muscles were left insensitive to the putative transmitters glutamate and aspartate when these were bath or iontophoretically applied. A low rate of mepsps persisted after late block, indicating that the muscles were still sensitive to the natural transmitters.     

<Emphasis Type="Italic">Fusarium</Emphasis> elicitor-dependent calcium influx and associated ros generation in tomato is independent of cell death

Fusarium oxysporum f. sp. lycopersici elicitor (EFOL-2) treatment induces cytosolic influx of calcium in Fusarium-resistant tomato suspension culture. The calcium signature was found to be biphasic, which is characteristic of recognition of oligosaccharides in the elicitor preparation. Further, several lines of evidence such as, (i) attainment of saturation level of the [Ca²⁺]_cyt at a definite extra-cellular calcium concentration (ii) prominent reduction in EFOL-2-induced influx in [Ca²⁺]_cyt on treatment with the calcium channel blockers verapamil and diltiazem and (iii) establishment of a refractory stage of [Ca²⁺]_cyt level upon repeated stimulation by EFOL-2, is indicative of receptor-mediated activation of the calcium channel for cytosolic elevation. In addition, inhibition of EFOL-2-induced [Ca²⁺]_cyt increase by protein kinase inhibitor staurosporine and wortmannin indicate phosphorylation is a regulatory event of calcium influx. Additionally, monitoring of cell death on EFOL-2 treatment indicated that the degree of ROS generation is not capable of inducing cell death. Inhibition of ROS generation on two separate occasions such as, calcium-free media and on treatment with inhibitors causing calcium channel occlusion revealed ROS generation as a successive event of calcium influx.     

Two classes of pyrethroid action in the cockroach

Pyrethroids are divided into two classes (Types I and II) based on their effects on the cercal sensory nerves recorded in vivo and in vitro and on the symptomology they produce in dosed cockroaches, Periplaneta americana. Type I compounds include pyrethrins, S-bioallethrin, [1R,cis]resmethrin, kadethrin, the 1R,trans and 1R,cis isomers of tetramethrin, phenothrin, and permethrin, and an oxime O-phenoxybenzyl ether. Electrophysiological recordings from dosed individuals reveal trains of cercal sensory spikes and sometimes also spike trains from the cercal motor nerves and in the CNS. Low concentrations of these pyrethroids act in vitro to induce repetitive firing in a cercal sensory nerve following a single electrical stimulus. This in vitro measurement, standardized for evaluating structure-activity relationships, shows that only 1R, insecticidal isomers are highly effective neurotoxins. The most potent compounds on the isolated nerve are [1R,trans]- and [1R,cis]tetramethrin, each active at 3 × 10^?13M. The poisoning symptoms of Type I compounds are restlessness, incoordination, hyperactivity, prostration, and paralysis. Type II compounds include [1R,cis,αS]- and [1R,trans,αS]cypermethrin, deltamethrin, and [S,S]fenvalerate. These α-cyanophenoxybenzyl pyrethroids do not induce repetitive firing in the cercal sensory nerves either in vivo or in vitro; moreover, they cause different symptoms, including a pronounced convulsive phase. Two other pyrethroids with an α-cyano substituent, i.e., fenpropathrin and an oxime O-α-cyanophenoxybenzyl ether, are classified as Type I based on their action on a cercal sensory nerve but the symptoms with these compounds resemble Type II. The two classes of pyrethroid action evident with the cockroach are discussed relative to their neurophysiological effects and symptomology in other organisms.     

Interaction of pyrethroids with mammalian spinal neurons

The effects of intravenous administration of non-cyano (cis-permethrin) and cyano-substituted (deltamethrin) pyrethroids were studied on spontaneous and evoked ventral root activity in rat spinal cord and on spontaneous firing of ventral horn interneurons in the cat. Both pyrethroids had dramatic facilitatory effects on spontaneous firing rates of ventral roots and spinal interneurons and increased the amplitude of mono- and polysynaptically mediated ventral root responses to dorsal root stimulation. Spontaneous and evoked afferent sensory activity was slightly enhanced by cis-permethrin, but not by deltamethrin. In the cat diazepam (0.5 mg/kg, iv) was equally effective in antagonizing the facilitation of interneuronal firing resulting from either deltamethrin or cis-permethrin. These effects of pyrethroids on spinal neurons may underly the production of tremor and choreoathetosis-salivation toxicity symptoms in mammals.     

Ca2+对Cd2+胁迫下板蓝根种子萌发及幼苗抗氧化酶活性的影响

研究了Cd²⁺（10 mg·L^-1、30 mg·L^-1）胁迫下不同浓度Ca²⁺（0、80、160、320 mg·L^-1）对板蓝根种子萌发、幼苗抗氧化酶系统及蛋白质含量的影响。结果表明：低浓度Ca²⁺（80、160 mg·L^-1）可缓解Cd²⁺毒害,显著提高板蓝根种子的发芽率、发芽势、发芽指数、活力指数,促进蛋白质含量的增加,提高SOD、POD、CAT活性,且160　mg·L^-1 Ca²⁺缓解效果最好,缓解能力随Cd²⁺浓度的升高有所下降;高浓度Ca²⁺（320 mg·L^-1）与Cd²⁺作用,反而抑制了板蓝根种子的萌发,幼苗的POD、SOD、CAT活性及蛋白质含量下降。低浓度Ca²⁺可以显著提高板蓝根的抗性,对Cd²⁺毒害起缓解作用,高浓度的Ca²⁺与Cd²⁺对板蓝根种子起协同毒害作用。     

The effects of two pyrethroids,cismethrin and deltamethrin,on skeletal muscle and the trigeminal reflex system in the rat

The actions of a cyano pyrethroid (deltamethrin) and a non-cyano pyrethroid (cismethrin) upon trigeminal motor reflexes and isolated muscle responses were studied in the rat. Deltamethrin caused a marked facilitation of the muscle response to nerve stimulation in pithed rats at 2.5 μmol kg⁻¹. In intact anaesthetised rats this was associated with abnormal repetitive EMG discharges and, at 4 μmol kg⁻¹ with a suppression of late components of the reflex response to sensory stimuli in the spinal trigeminal nucleus and trigeminal motor nucleus. In contrast cismethrin had no effect on the muscle response to direct nerve stimulation at up to 15 μmol kg⁻¹, but produced abnormal extra responses to sensory stimuli in the trigeminal ganglion, spinal and motor nuclei, and jaw muscles at 9 μmol kg⁻¹. It is concluded that whilst deltamethrin produces reflex excitation within the trigeminal system at a primarily muscular site, cismethrin produces excitation at all stages of the reflex loop. This contrast is consistent with the known difference in duration of sodium current prolongation produced by the two pyrethroids. These findings, together with other known central actions of deltamethrin suggest that it has multiple sites of action in the intact animal, both central and peripheral, whilst most of the simpler symptoms produced by cismethrin may adequately be explained by action at a reflex level.