Robert M. Hollingworth

Global pesticide resistance in arthropods.

Global pesticide resistance in arthropods , Global pesticide resistance in arthropods , کتابخانه دیجیتال جندی شاپور اهواز

Mode of action of bullatacin: A potent antitumor and pesticidal Annonaceous acetogenin

Bullatacin, a compound isolated from plants of the Annonaceae, and its analogues show in vivo potential as antitumor agents based on their efficacy in normal mice bearing L1210 murine leukemia and athymic mice bearing A2780 conventional ovarian cancer xenografts. These compounds also have interesting potential as insecticides and inhibit respiration in insect-derived Sf9 cells with high potency. Their toxicity in both cases probably arises from their strong inhibition of mitochondrial electron transport with a specific action at complex I.

Defining Terms for Proactive Management of Resistance to Bt Crops and Pesticides

ABSTRACT Evolution of pest resistance to pesticides is an urgent global problem with resistance recorded in at least 954 species of pests, including 546 arthropods, 218 weeds, and 190 plant pathogens. To facilitate understanding and management of resistance, we provide definitions of 50 key terms related to resistance. We confirm the broad, long-standing definition of resistance, which is a genetically based decrease in susceptibility to a pesticide, and the definition of “field-evolved resistance,” which is a genetically based decrease in susceptibility to a pesticide in a population caused by exposure to the pesticide in the field. The impact of field-evolved resistance on pest control can vary from none to severe. We define “practical resistance” as field-evolved resistance that reduces pesticide efficacy and has practical consequences for pest control. Recognizing that resistance is not “all or none” and that intermediate levels of resistance can have a continuum of effects on pest control, we describe five categories of field-evolved resistance and use them to classify 13 cases of field-evolved resistance to five Bacillus thuringiensis (Bt) toxins in transgenic corn and cotton based on monitoring data from five continents for nine major pest species. We urge researchers to publish and analyze their resistance monitoring data in conjunction with data on management practices to accelerate progress in determining which actions will be most useful in response to specific data on the magnitude, distribution, and impact of resistance.

Differences in oxidative dearylation and desulfuration of fenitrothion by cytochrome P-450 isozymes and in the subsequent inhibition of monooxygenase activity

Abstract The organophosphorus insecticide, fenitrothion ( O,O -dimethyl O -(3-methyl-4-nitrophenyl) phosphorothioate), a substrate for the cytochrome P -450 ( P -450) monooxygenase system, yields the corresponding phosphate triester (fenitroxon) by oxidative desulfuration (an activation reaction) and 4-nitro- m -cresol by oxidative dearylation (a detoxication reaction). Four constitutive P -450 isozymes and the major isozymes induced by phenobarbital (PB) and β-naphthoflavone (BNF) were incubated with [ 14 C]fenitrothion in reconstituted monooxygenase systems. Both metabolites were formed with all isozymes, with the ratio of oxon to cresol being characteristic of the individual P -450s. Cytochrome P -450 B2 and P -450 PB formed the highest percentage of oxon, 75 and 82%, respectively; while P -450 A1, B3, and BNF produced 55 to 60% oxon. By contrast, P -450 A2 formed the least amount of oxon, 38%, with 62% of the product being 4-nitro- m -cresol. Microsomes prepared from mice treated in vivo with organophosphates, such as fenitrothion, have reduced levels of cytochrome P -450 and associated monooxygenase activities. Presumably, this reduction is due to destruction of P -450 caused by the release of active sulfur occurring during desulfuration. To determine if some P -450 isozymes were preferentially inhibited by fenitrothion, purified isozymes were incubated with fenitrothion and subsequent p -nitroanisole O -demethylase activity was determined. Inhibition studies using purified P -450 isozymes indicated close to 100% inhibition by fenitrothion of P -450 PB, while enzyme activity of P -450 BNF and P -450 A2 was inhibited 85–90%.

Resistance of codling moth, Cydia pomonella (L.) (Lepidoptera: Tortricidae), larvae in Michigan to insecticides with different modes of action and the impact on field residual activity.

BACKGROUND The codling moth is one of the principal pests of apple in the world. Resistance monitoring is crucial to the effective management of resistance in codling moth. Three populations of codling moth in neonate larvae were evaluated for resistance to seven insecticides via diet bioassays, and compared with a susceptible population. In addition, apple plots were treated with labeled field rate doses of four insecticides. Treated fruit were exposed to neonate larvae of two populations from commercial orchards. RESULTS Two populations of codling moth expressed two- and fivefold resistance to azinphos-methyl, seven- and eightfold resistance to phosmet, six- and tenfold resistance to lambda-cyhalothrin, 14- and 16-fold resistance to methoxyfenozide and sixfold resistance to indoxacarb, but no resistance to acetamiprid and spinosad. The impact of the resistance to azinphos-methyl, measured as fruit damage, increased as the insecticide residues aged in the field. In contrast, fruit damage in methoxyfenozide- and lambda-cyhalothrin-treated fruit was observed earlier for resistant codling moth. No differences in efficacy were found for acetamiprid. CONCLUSIONS Broad-spectrum insecticide resistance was detected for codling moth. Resistance to azinphos-methyl, lambda-cyhalothrin and methoxyfenozide was associated with reduced residual activity in the field. Broad-spectrum resistance presents serious problems for management of the codling moth in Michigan.

The Sf9 cell line as a model for studying insect octopamine-receptors

Abstract Adenylate cyclase-coupled octopamine (OA) receptors were demonstrated in the Sf9 insect cell line derived from Spodoptera frugiperda . This receptor-enzyme complex is membrane-associated, has a requirement for GTP and is forskolin-sensitive. In intact Sf9 cells, 100 μM OA produces a 3-fold increase in cyclic AMP (cAMP) levels. These cells do not exhibit adenylate cyclase sensitive to dopamine or serotonin. This binding site shows a high affinity for OA ( K a = 3.5 μ M), the formamidine, N -demethylchlordimeform, DCDM ( K a = 0.3 μ M) and the imidazoline, 2,3-xylylaminomethyl-2′-imidazoline, XAMI ( K a = 0.7 μ M) with a reduced affinity for α 2 -selective agonists such as clonidine and UK-14304. Of 24 putative antagonists tested in this system, ergotamine, phentolamine, (+)mianserin and RX821002A were the most effective. Other antagonists such as yohimbine, propranolol and (+)butaclamol were relatively ineffective. These responses differ considerably from the pharmacological profile for the cockroach nerve cord octopamine-sensitive adenylate cyclase (OSAC) but are similar to previous results with the lepidopteran, Manduca sexta . There appears to be a closer pharmacological relationship of the Sf9 and cockroach OA receptor to the vertebrate imidazoline-preferring receptor (IPR) than the α 2 -adrenergic receptor. Studies on receptor dynamics indicated that the Sf9 OSAC undergoes agonist-induced desensitization. Therefore, based on these combined data, we propose the Sf9 cell line as a convenient model system for studying the pharmacology and dynamics of lepidopteran adenylate cyclase-coupled OA receptors.

Characterization of a potent agonist of the insect octopamine-receptor-coupled adenylate cyclase

Abstract The imidazoline, 2,3-xylylaminomethyl-2′-imidazoline (XAMI) was evaluated for its effects on octopamine-sensitive adenylate cyclase (OSAC) in crude membrane preparations of neural and non-neural tissues of the American cockroach, Periplaneta americana and ventral-nerve cord homogenates of the tobacco hornworm, Manduca sexta . In the cockroach nerve cord, XAMI was found to be a partial agonist with a V max 80% of p -octopamine (OA) and a K a of 30 nM. The affinity is 185 times greater than that of OA. Additivity studies suggest that at maximally stimulating concentrations, XAMI interacts primarily with the OSAC. The antagonist profile for XAMI mimics that of OA with mianserin being the best antagonist, followed by the α-adrenergic antagonist phentolamine. These antagonists were shown to act competitively at the XAMI-binding site. β-adrenergic and dopaminergic antagonists were ineffective. These data indicate that XAMI has the highest reported affinity of any OA-receptor agonist and may be a suitable ligand for studies of the OA receptor.

Agonist-induced desensitization of an octopamine receptor

The octopamine-sensitive adenylate cyclase associated with haemocytes of the American cockroach, Periplaneta americana, has been used as a model system with which to study desensitization of the octopamine receptor. Preincubation of the haemocytes with octopamine results in a large decrease in subsequent maximal stimulation of cyclic AMP production by octopamine with little change in affinity of the receptor for the agonist. This effect of preincubation is dependent upon the concentration of octopamine in the preincubation media and on the duration of exposure. The attenuation appears to be a receptor-mediated event rather than an artifact of the preincubation. Octopamine receptor agonists (octopamine, synephrine, N-demethylchlordimeform) induce desensitization while biogenic amines with poor octopamine receptor affinity (dopamine, serotonin, norepinephrine) are without affect. In contrast, the octopamine receptor antagonist, phentolamine, appears to enhance subsequent stimulation by octopamine. The attenuation of octopamine stimulation of adenylate cyclase is conserved in broken-cell preparations with no alteration of responses to NaF or forskolin. Incubation of the cells with dibutyryl cyclic AMP or forskolin does not induce desensitization. The data indicate that the OA receptors coupled to AC in cockroach haemocytes undergo an homologous desensitization in response to exposure to agonists.

Localization and pharmacological characterization of nicotinic-cholinergic binding sites in cockroach brain using α- and neuronal bungarotoxin

Abstract [ 125 I]α-Bungarotoxinisusedasaprobetostudythenicotinic-cholinergicreceptorinmembrane preparations of the cockroach brain. Binding is restricted mainly to particulate fractions of brain homogenates, is time dependent and is saturable above 2 nM with very low non-specific binding. Scatchard analysis indicates that binding is associated with a single affinity site ( K d = 1.09 nM) having a B max of 8926 fmol/mg protein which is the highest concentration of binding sites yet reported in insects. Association kinetics are best fit by a mono-exponential model with a k obs = 4.37 × 10 −3 s −1 . Dissociation is best described by a bi-exponential model giving dissociation constants of 1.18 × 10 −5 and 9.94 × 10 −5 s −1 . The K d s calculated from kinetic data are 0.029 and 0.25 nM suggesting the possibility of heterogeneous binding sites not detected by saturation studies. Displacement studies indicate that binding follows a nicotinic pharmacology and demonstrate the high affinity of methyllycaconitine and the anthelmintics, morantel and pyrantel. Displacement by neuronal bungarotoxin shows the presence of two distinct binding sites not differentiated by α-bungarotoxin. Autoradiographic studies show α-bungarotoxin to be binding to neuropile regions of the brain, to be displaced from these regions by agents effective in binding studies and demonstrate that the neuronal bungarotoxin binding sites can be regionally localized.

CHAPTER 57 – Inhibitors and Uncouplers of Mitochondrial Oxidative Phosphorylation

Oxidative phosphorylation (oxphos) is the primary process by which the energy derived from the catabolism of carbohydrates, fats, and proteins is used to synthesize ATP in virtually every cell of eukaryotic organisms. Compounds that have a primary action on oxphos have a long history of use to control pests. Today, compounds that disrupt oxphos in the target species are widely used as fungicides and have important uses as insecticides and acaricides. This chapter discusses the toxicology of compounds that have their most important primary toxic effect on oxphos in vertebrates or have a primary effect on mitochondrial oxphos in target species with a probability of similar action in vertebrates. It describes the cell structures and mechanisms involved in oxphos and ATP synthesis, and the different ways by which pesticides can disrupt oxphos and hence cause damage to cells and tissues. Mechanisms by which oxphos is disrupted by pesticides include: inhibiting the operations of the electron transport chain; preventing the electrochemical potential gradient from being coupled to ATP synthesis; blocking the ATP synthase machinery; diverting electrons from the electron transport chain and generating reactive oxygen species (ROS); and arsenolysis. The chapter describes the toxicological consequences of disrupting oxphos by pesticide action and their relevance for toxicity, and provides details of the general properties, uses, and toxicological profiles of several pesticides.