DDT receptor

Critical Fit at Site of Action - The present views of the action of DDT strongly support a precise physical Interaction between a macro-molecular element of the nerve axon, the "DDT-receptor", and the DDT-type molecule . Analogues isosterlc with DDT (1 and with appropriate lipo-... 

Hurst (19) discusses the similarity in action of the pyrethrins and of DDT as indicated by a dispersant action on the lipids of insect cuticle and internal tissue. He has developed an elaborate theory of contact insecticidal action but provides no experimental data. Hurst believes that the susceptibility to insecticides depends partially on the cuticular permeability, but more fundamentally on the effects on internal tissue receptors which control oxidative metabolism or oxidative enzyme systems. The access of pyrethrins to insects, for example, is facilitated by adsorption and storage in the lipophilic layers of the epicuticle. The epicuticle is to be regarded as a lipoprotein mosaic consisting of alternating patches of lipid and protein receptors which are sites of oxidase activity. Such a condition exists in both the hydrophilic type of cuticle found in larvae of Calliphora and Phormia and in the waxy cuticle of Tenebrio larvae. Hurst explains pyrethrinization as a preliminary narcosis or knockdown phase in which oxidase action is blocked by adsorption of the insecticide on the lipoprotein tissue components, followed by death when further dispersant action of the insecticide results in an irreversible increase in the phenoloxidase activity as a result of the displacement of protective lipids. This increase in phenoloxidase activity is accompanied by the accumulation of toxic quinoid metabolites in the blood and tissues—for example, O-quinones which would block substrate access to normal enzyme systems. The varying degrees of susceptibility shown by different insect species to an insecticide may be explainable not only in terms of differences in cuticle make-up but also as internal factors associated with the stability of oxidase systems. 

Resistance to DDT has been developed in many insect species. Although there are some cases of metabolic resistance (e.g., strains high in DDT dehydrochlorinase activity), particular interest has been focused on kdr and super kdr mechanisms based upon aberrant forms of the sodium channel—the principal target for DDT. There are many examples of insects developing resistance to dieldrin. The best-known mechanism is the production of mutant forms of the target site (GABA receptor), which are insensitive to the insecticide. 

Veratridine appears to act at a different part of pore channel from DDT or pyrethroids Act as agonists causing desensitization of receptor Inhibitor of GABA receptors... 

For the last forty years, many reports have emerged on the hormone-like effects of chemical compounds such as pesticides and industrial chemicals upon wildlife and humans. The effects of these materials are believed to be either direct or indirect. Direct effects involve positive or negative interactions with the hormone receptors. Indirect effects may result when the synthesis of hormones or their receptors is altered, or the transport, metabolism, or elimination of hormones is modified in some way. The discovery of hormone-like properties of some compounds was made long after their release into the environment. It was shown soon after their introduction that aviation crop dusters handling DDT had low sperm counts and workers at a plant producing the insecticide kepone were reported to have low libido, sperm counts and to be impotent. Subsequently, experiments conducted in laboratory animals demonstrated unambiguously the oestrogenic activity of these pesticides. 9 refs. 

Tests for specific classes of chemicals include the measurement of transmitter stimulated adenyl cyclase and Na/K-ATPase for chemicals that affect receptor function or cholinesterase inhibition for organophosphates or carbamates. Electrophysiological techniques may detect chemicals such as DDT or pyrethroids, which affect impulse transmission. 

The action spectrum for DDT and its structural analogs is known to be quite broad and cannot be attributed to simple enzyme inhibition, as in the case of the carbamates or the organophosphates. The presence of chloroaryl moieties, as well as steric effects at receptor sites, both appear to be factors affecting insecticidal activity. In addition to DDT itself, its metabolites DDE and DDA and DDD have some activity. Efforts to overcome insect resistance and to produce more biodegradable analogs led to the introduction of substituents other than chlorine for... 

In addition to stealth strategies, other more specific approaches include the removal of undesired ligands on the DDTS which interact with specific receptors on non-target cells. 

The biological activities of steroid hormones result from interactions with specific receptors. For example, estradiol interacts with the estrogen receptor. Some industrial chemicals, such as DDT, bisphenol A, and polychlorinated biphenyls, may possibly interact with these receptors and cause hormonal effects on people and wildlife. 

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