Receptor scenarios

Belleau has offered a detailed consideration of the single receptor situation which allows explanation of the actions of agonists, antagonists and agents of mixed activities/41  

Although the evidence for the dual model is compelling and difficult to explain on the basis of the single receptor scenario, it must be borne in mind that the use of ligands that bind in a covalent manner in receptor studies inevitably involves displacement of normal equilibria in an irreversible sense. Conclusions drawn from such experiments may therefore not be relevant to the natural physiological conditions/43  

OVERALL STRUCTURE-ACTIVITY RELATIONSHIPS OF OPIOID LIGANDS 

In an attempt to impose some order upon the heterogeneous molecular nature of opioids, it is convenient to subdivide them broadly into five groups, as follows, of which the peptide category has come to the fore only since 1975  

Polycyclic molecules of the morphine, morphinan, and benzomorphan type. 

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Once the source-pathway-receptor scenarios have been identified the risks associated with each one can be assessed qualitatively (i.e. descriptively). Guidance on assigning the likelihood and consequences to the scenarios is given in Tables 6.1-6.3. 

The first step in any assessment of a site affected by ground gas or vapours is to construct a conceptual model. The desk study and site investigation data should be used to develop this. The first part of the gas risk assessment is to use the model to identify any source pathway and receptor linkages from the conceptual model. If there is no linkage then there is no risk. Once the source-pathway-receptor scenarios have been identified the risks associated with each one can be assessed qualitatively (i.e. descriptively). 

Dispersion modeling of credible worse case scenarios indicates the one-hour exposure to nearest human receptor exceeds ERPG-2 level or equivalent. 

It is worth examining the possible magnitudes of the error with various scenarios. The maximal value for [A]/Ka can be approximated, assuming a system where response is directly proportional to receptor occupancy. Under these circumstances, Response = 0.3 = [A]/Ka/([A]/Ka + 1), which in this case is [A]/Ka = 0.5. Therefore, the pA2 is pKB + Log (2) (i.e., the pA2 will overestimate the affinity of the antagonist by a maximal factor of 2). If the insurmountable antagonist is allosteric antagonist that reduces the affinity of the receptor for agonist (a < 1), then the error will be <2. However, if the modulator... 

Data from chemical characterization were used to estimate possible adverse effects on humans and the environmental receptors. Following previously published works [11, 19], a hypothetic scenario was set up to assess the risk posed by these non-conventional matrix an accidental leachate release into ground-water resulting in 1 100 and 1 1,000 dilutions of the leachate compounds, which have been subjected to dilution as the leachate mixes with the groundwater (Fig. 3). 

All steps of the Ras pathway from ligand binding to receptor tyrosine kinases, down to activation of effectors like Raf kinase, occur at the plasma membrane. However, most biophysical studies on protein/protein interactions involved in this scenario have been carried out with bacterially synthesized proteins lacking... 

The next step is impact prediction that requires detailed quantitative information about the sources of risk agents, exposure models, the receptors and possible changes in the state of these receptors caused by the defined agents. If the CLL concept was selected for assessment ecosystem effects it should firstly be utilized for impact baseline studies or assessing the do-nothing scenario. In this context CLL calculation includes the following steps (Bashkin, 2002) ... 

Worst-case scenario. When considering the stationary source s worst-case scenario, there are selection factors to be considered. In addition to the largest inventories of a substance, the following conditions must also be considered smaller quantities handled at higher process temperatures and pressures, and proximity to the boundary of the stationary source. Sources must analyze and report additional worst-case scenarios for a hazard class if the worst-case scenario from another covered process affects a different set of public receptors than the original worst-case scenario. It is interesting to note that worst-case release data indicate that the distances and thus the populations that could be threatened are greater for toxic substances than for flammable substances. 

Estimating distances. For both the worst-case and alternative release scenarios, the source must estimate the distance to where the endpoint is no longer exceeded and estimate the population (rounded to two significant digits) within a circle defined by the distance and centered at the release point. U.S. Census data may be used and it does not have to be updated however, the presence of sensitive populations (e.g. hospitals, schools, etc.) must be noted. In addition, the source must identify and list the types of environmental receptors within the calculated worst-case distance and circle however,... 

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