Other Target Sites

There is no experimental evidence to demonstrate that other reactions in plant carotenogenesis, whether they are related directly to enzyme activity or not, are target sites of the current range of bleaching herbicides. It is feasible that compounds such as amitrole and CPTA may act at multiple sites or on reactions which cannot be assayed at the present time. 

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Other target sites for certain pyrethroids include the voltage-gated calcium and chloride channels. Of particular interest is the increased effect of Type II pyrethroids on certain phosphoforms of the N-type Cav2.2 calcium channel following post-translational modification and its relationship to enhanced neurotransmitter release seen in vivo. 

Immunotoxicity is of particular concern for substances that induce toxicity on the immune system at dose levels below those which induce toxicity at other target sites (WHO/IPCS 1996). 

Current weight-of-evidence approaches for Pb show that we cannot assume that a single somatic target exists for Pb while all other target sites function with littie or less sensitive responses at a given level of human exposure. Lead produces low-dose toxicity in multiple body sites and the respective threshold doses, i.e., critical doses, for onset of toxicity do not differ greatly. 

Apart from the wide range of neurotoxic and behavioral effects caused by OPs, many of which can be related to inhibition of AChE, other symptoms of toxicity have been reported. These include effects on the immune system of rodents (Galloway and Handy 2003), and effects on fish reproduction (Cook et al. 2005 Sebire et al. 2008). In these examples, the site of action of the chemicals is not identified. Indirect effects on the immune system or on reproduction following initial interaction with AChE of the nervous system cannot be ruled out. It is also possible that OPs act directly on the endocrine system or the reproductive system, and phosphorylate other targets in these locations (Galloway and Handy 2003). 

Some of the best evidence of links between effects at different organizational levels comes from studies with OPs, where levels of AChE inhibition have been compared with associated neurophysiological and behavioral effects. In adopting this approach, however, the picture is complicated by mounting evidence for these compounds acting on target sites other than AChE, as discussed in Section 16.3. Thus, behavioral disturbances caused by an OP may be the outcome of interaction with both AChE and one or more other sites of action. The following account, however, will be concerned with situations where effects of OPs are closely related to levels of AChE inhibition. More complex scenarios will be discussed in the next section. 

Three amines—dopamine, norepinephrine, and epinephrine—are synthesized from tyrosine in the chromaffin cells of the adrenal medulla. The major product of the adrenal medulla is epinephrine. This compound constimtes about 80% of the catecholamines in the medulla, and it is not made in extramedullary tissue. In contrast, most of the norepinephrine present in organs innervated by sympathetic nerves is made in situ (about 80% of the total), and most of the rest is made in other nerve endings and reaches the target sites via the circu-... 

Society for Endocrinology http //www.endocrinology.org (Aims to promote advancement of public education in endocrinology. Contains a number of articles on endocrinology and a list of links to other relevant sites.) tbase—the Transgenic/Targeted Mutation Database at the Jackson Laboratory, Bar Harbor, Maine http //tbase.jax.org/... 

These mechanisms of resistance rely on reducing or preventing access of antibiotic to their target sites, but other mechanisms of resistance involving the target sites themselves can be considered. Alterations in the target site which reduce the binding of... 

RES-Avoiding Liposomes. Since intravenously administered liposomes tend to accumulate in the RES, liposomal drugs work effectively when the target site is the RES. On the other hand, when the target site is not the RES, liposomal uptake by RES should be avoided. Liposomes that are not recognized by the RES have... 

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