Behavioral effects AChE action

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. 

It should be further noted that the effects of nerve agents on GABAergic transmission in the CNS may have imph-cations for behavioral effects in laboratory animals and humans, and may also contribute to the induction of convulsions at higher doses (Bakshi et al, 2000). Nevertheless, given the present undefined application of non-cholinergic data to whole-body estimations, reliance on the primary assumption of AChE action is consistent with recognized opinion (Bakshi et al, 2000). 

The fact that the differential sensitivity of young animals is end point specific, however,. shows that simple kinetic parameters will not provide a full explanation for all age-related differences. As mentioned previously, many cholinesterase-inhibiting pesticides act at other neuronal sites (e.g., muscarinic and/or nicotinic receptors) in addition to the AChE enzyme. Since the expression of these receptors and/or actions develops at different rates (Karanth and Pope. 2003 Tice et ai, 1996), the age-related differences in the behavioral profile of a specific pesticide may be a function of the cholinergic receptors, if any, that it directly affects, Thus, whereas the toxicokinetic factors for different pesticides predict age-related differences in cholinesterase inhibition, it appears that toxicodynamic differences may have a greater influence on the behavioral effects. 

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