Curve dose-response

Fig. 8. Agonist, dose—response curves, (a) For an agonist where a value of 10 M is indicated at the concentration giving 50% response, (b) For an agonist alone, Aq, and in the presence of increasing amounts of irreversible receptor antagonists, B—F. There is a progressive rightward shift of the dose—response curve prior to reduction of maximum response. This pattern is consistent with the presence of a receptor reserve.

A critical component of the G-protein effector cascade is the hydrolysis of GTP by the activated a-subunit (GTPase). This provides not only a component of the amplification process of the G-protein cascade (63) but also serves to provide further measures of dmg efficacy. Additionally, the scheme of Figure 10 indicates that the coupling process also depends on the stoichiometry of receptors and G-proteins. A reduction in receptor number should diminish the efficacy of coupling and thus reduce dmg efficacy. This is seen in Figure 11, which indicates that the abiUty of the muscarinic dmg carbachol [51 -83-2] to inhibit cAMP formation and to stimulate inositol triphosphate, IP, formation yields different dose—response curves, and that after receptor removal by irreversible alkylation, carbachol becomes a partial agonist (68). 

Fig. 11. Dose—response curves for (A,A) inhibition of cyclic AMP formation and stimulation of IP formation by carbachol (A,D) before and (A,H) after reduction of receptor number by irreversible alkylation (carbachol) is in M. Error bars ( ) are shown for some studies.

R. J. Taharida and L. S. Jacob, The Dose—Response Curve in Pharmacology, Springer Vedag, New York, 1979. 

Fig. 5. Toxic chemical dose—response curves (a) no effect (b) linear effect (c) no effect at low dose and (d) beneficial at low dose.

The biological response line for acute respiratory disease is a dose-response curve, which for a constant concentration becomes a duration-response curve. The shape of such a curve reflects the ability of the human body to cope with short-term, ambient concentration respiratory exposures and the overwhelming of the body s defenses by continued exposure. 

However, there are multiple routes of entry to the body for some materials. When a toxic chemical acts on the body or system, the nature and extent of the injurious response depends upon the dose received, that is, the amount of the chemical actually entering the body or system. This relationship of dose and response is shown in Figure 3. The dose-response curve varies with the type of material and the response. 

Hazard characterization, or dose-response characterization, by using experimental animals to reveal target organs and toxic doses, and the shape of the dose-response curve... 

FIGURE 5.56 The threshold region for chronic dose-response curves. [Reprinted with permission from Tardiff, R.G., and Rodricks, J.V. (1987). (Eds.), Toxic Substances and Human Risks Principles of Data Interpretation. New York Plenum Press.]... 

To.xicity values for carcinogenic effects can be e.xprcsscd in several ways. The slope factor is usually, but not always, the upper 95th percent confidence limit of the slope of the dose-response curve and is e.xprcsscd as (mg/kg-day). If the extrapolation model selected is the linearized multistage model, this value is also known as the ql. That is ... 

Describe and illustrate the process of setting a reference dose (RfD) using a schematic dose response curve. Correctly label the axis and all other important information. 

If the exposure level (E) exceeds tliis tlireshold (i.e., E/RfD exceeds unity), tliere may be concern for potential noncancer effects. As a rule, tlie greater tlie value of E/RfD above unity, tlie greater tlie level of concern. However, one should not interpret ratios of E/RfD as statistical probabilities a ratio of 0.001 does not mean tliat tliere is a one in one tliousand cliance of the effect occurring. Furtlier, it is important to empliasize tliat tlie level of concern does not increase linearly as tlie RfD is approached or exceeded because RfDs do not have equal accuracy or precision and are not based on tlie same severity of toxic effects. Thus, tlie slopes of the dose-response curv e in excess of the RfD can range widely depending on tlie substance. 

The LCjj concept is visualized in the dose-response curve presented in Figure 4-114 [32A]. The dose or concentration is plotted on the abscissa, and... 

Figure 4-114. Determination of lethal toxicity from the dose-response curve [32A]. (Courtesy SPE.)...

Dose-response curves depict the response to an agonist in a cellular or subcellular system as a function of the agonist concentration. Specifically, they plot response as a function of the logarithm of the concentration. They can be defined completely by three parameters namely, location along the concentration axis, slope, and maximal asymptote... 

FIGURE 1.12 Dose-response curves. Any dose-response curve can be defined by the threshold (where response begins along the concentration axis), the slope (the rise in response with changes in concentration), and the maximal asymptote (the maximal response). 

FIGURE 1.15 Dose-response curves. Dose-response curve to an agonist that produces 80% of the system maximal response. The EC50 (concentration producing 40% response) is 1 pM, the EC25(20%,) is 0.5 pM and the ECg0 (64%) is 5 jiM. 

Dose-response curves quantify drag activity. The maximal asymptote is totally dependent on efficacy, while potency is due to an amalgam of affinity and efficacy. 

FIGURE 2.2 Binding and dose-response curves for human calcitonin on human calcitonin receptors type 2. (a) Dose-response curves for microphysiometry responses to human calcitonin in HEK cells (open circles) and binding in membranes from HEK cells (displacement of [,25I]-human calcitonin). Data from [1]. (b) Regression of microphysiometry responses to human calcitonin (ordinates) upon human calcitonin fractional receptor occupancy (abscissae). Dotted line shows a direct correlation between receptor occupancy and cellular response. 

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