Cellular sites of actions

Broadly speaking, toxic interactions between chemicals and cellular sites of action are of two kinds ... 

In other chapters of this volume considerable attention is given to marine toxins whose cellular sites of action have been identified. For example, saxitoxin, brevetoxin, and sea anemone toxins are prototypes of toxic molecules whose chemical structure is known, and whose actions on ionic channels in the cell membrane have been elucidated. Recent additions to such toxins are the piscivorus cone... 

Carmines EL, Carchman RA, Borzelleca JF. 1979. Kepone Cellular sites of action. Toxicol Appl Pharmacol 49 543-550. 

Each drug is chosen to have a different cellular site of action or different cell cycle specificity. 

A toxicant must be present at its cellular site of action in sufficient amounts to exert its deleterious effects. When the concentration is too small it is said that the threshold has not been reached therefore, the material does not exert any adverse action. The distribution of active substances in the body is not uniform, and certain cells can exhibit preferentially high affinities for particular agents. Pharmacokinetic thresholds determine the effective dose of a chemical at its biological target site based on the absorption, distribution, biotransformation, and excretion of the particular chemical. 

Protox is thought to be a membrane-bound enzyme probably in or on the plastid envelope (Fig. 6). Fluorescence microscopy of achlorophyllous tissues treated with acifluorfen in darkness, results in strong porphyrin fluorescence in both plastids and cytoplasm, whereas, fluorescence was localized almost exclusively in plastids of untreated cells (fi8). PPIX concentrations were almost 200-fold greater in treated than untreated tissues. These data suggest that PPIX leaks from plastids or plastid envelopes of treated tissues and that this leakage is independent of membrane damage due to lipid peroxidation. Thus, as in our previous model (2S)> the cellular site of action of these herbicides may be the plastid envelope. 

The complexity of neural, endocrine, and paracrine regulation is illustrated in the following table, which displays ligands that have been shown to affect gastric add secretion by direct action on gastric mucosal cells as well as their probable cellular site of action. 

Most of the organic pollutants described in the present text act at relatively low concentrations because they, or their active metabolites, have high affinity for their sites of action. If there is interaction with more than a critical proportion of active sites, disturbances will be caused to cellular processes, which will eventually be manifest as overt toxic symptoms in the animal or plant. Differences between species or strains in the affinity of a toxic molecule for the site of action are a common reason for selective toxicity. 

In the light of such considerations, it is possible to discuss toxins which have already been analyzed in terms of their sites of action. Such a discussion is best conducted by categorizing the various possible cellular sites at which a toxin might act. The most obvious sites are the membrane channels for ions, receptors for neurotransmitters, membrane pumps, and the membrane itself. Invertebrate toxins acting on membrane channels include the conotoxins (10) and several of the sea anemone toxins (97). 

It is quite possible that phenolic acids may produce more than one effect on the cellular processes responsible for mineral absorption. The potential sites of action discussed above all involve cellular membranes in some way. Which mechanism of action is predominant in a given situation may depend upon the concentration of allelochemicals present and the conditions (e.g. pH) of the plant/chemical interaction. 

The neuroeffector roles of OA may be broadly classified as those in which it acts as a neurotransmitter, as a neuromodulator, and as a neurohormone (12). The distinction between these actions is not absolute, but a neurotransmitter, released into a synapse, tends to have a rapid, highly localized action on a neighboring cell, while a neurohormone tends to have a slower, more prolonged action on a large number of cellular elements, often at a considerable distance from the point of its release. A neuromodulator is a neurohormone, released locally or at a distance from its site of action, that regulates the excitability of another nerve, muscle or gland cell. 

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