Sensitivity of target sites

Although implicated less frequently in arthropod pesticide resistance, diminished sensitivity of target sites in the nervous system is a major factor in many cases of resistance to different classes of insecticides. As more is learned about this phenomenon, we may find that it plays a more important role in resistance than is currently known. There are two major types of target site insensitivity. Uith insecticides such as DDT, certain other... 

Modification of target sites Alteration of the target site through mutation can confer resistance as occurs with the penicillin binding proteins in methicillin-resistant aureus, or the enzyme dihydrofolate reductase, which is less sensitive to inhibition in organisms resistant to trimethoprim. 

Our preliminary results with fish brain preparations suggest that ion flux techniques may be valuable in studies of target site differences between species. We have demonstrated veratridine-stimulated, tetrodotoxin-sensitive sodium uptake in a vesicular preparation from fish brain, thus confirming the presence of functional sodium channels in this preparation. Our results with , -DDT in this system also agree well with the action of DDT analogs and pyrethroids in mouse brain assays. Further studies wih both preparations should allow the exploration of target site differences between mammals and fish that have been inferred from whole animal toxicity studies. 

Various cellular contents analysed,showed significant increase in all the macromolecular contents viz. DNA, RNA Protein, lipids and phospholipids of the EDDP-resistant mutants of P. oryzae and IK oryzae. The efflux of electrolytes was reduced in the resistant mutants when compared to control. In interpreting the results, it should be realized that the phospholipids, the target site of inhibition for edifenphos seem to be unaffected in the mutants as evidenced from the higher values of phosphatidylcholine compared sensitive strain. These data indicate that the mechanism of resistance to edifenphos is not related to the target site of edifenphos. De waard and Van Nistelrooy(38) also reported that the mechanism of resistance in J . oryzae to pyrazophos (PP) was not related to the change of target site of PP. It seems probable that resistance in P oryzae and IK oryzae to edifenphos... 

Pyrethroids have low oral toxicity to mammals, and in general their insect (topical) to mammal (oral) toxicity ratio is much higher than that of the other major classes of insecticides [25]. As the reason, at least the following mechanisms are conceivable (1) negative temperature dependence - differences in body temperature between insects and mammals makes the insect nerves much more sensitive, (2) metabolic rate - insects metabolize the insecticide more slowly than mammals, and the metabolizing enzyme systems are different, and (3) differences in body size - insects will have less chance to metabolize the insecticides before reaching the target site [26]. 

When comparisons are made between populations, both the effectiveness of the membrane barrier in R fish and the sensitivity of the target site can be demonstrated (Table V). When endrin Ss/Rs ratios are compared, the ratio is less than 1 this suggests that more insecticide is required to elicit symptoms in the R than in the S fish. 

We have, therefore, been able to indirectly assess the importance of three factors involved in chlorinated alicyclic insecticide resistance in mosquitofish disposition, metabolism and target site sensitivity. In a highly polluted environment in which mosquitofish have been placed under severe selective pressures by chronic exposure to insecticides, the system of metabolism appears to be of little significance in resistance the... 

PARP-1 in vitro. The insulator function of most of the same CTCF target sites was sensitive to the general PARP inhibitor 3-aminobenzamide. Collectively, these results support a role for PAR and PARP(s) in the activity of insulators, with an insulator-bound protein, possibly CTCF, as a target for PARylation. 

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