Schild plots

A plot of log([A]g j[A — 1) versus log[B], called a Schild plot, yields a straight line of unit slope and intercept of iCg, the latter often expressed on a scale analogous to that for pH, so that = logif (46—48). 

FIGURE 6.6 Schilcl regression for pirenzepine antagonism of rat tracheal responses to carbachol. (a) Dose-response curves to carbachol in the absence (open circles, n = 20) and presence of pirenzepine 300 nM (filled squares, n = 4), 1 jjM (open diamonds, n=4), 3j.lM (filled inverted triangles, n = 6), and 10j.iM (open triangles, n = 6). Data fit to functions of constant maximum and slope, (b) Schild plot for antagonism shown in panel A. Ordinates Log (DR-1) values. Abscissae logarithms of molar concentrations of pirenzepine. Dotted line shows best line linear plot. Slope = 1.1 + 0.2 95% confidence limits = 0.9 to 1.15. Solid line is the best fit line with linear slope. pKB = 6.92. Redrawn from [5],... 

More usually, both (r - 1) and [B] are plotted on logarithmic scales (the Schild plot). The outcome should be a straight line with a slope of unity, and the intercept on the x-axis provides an estimate of log KB. The basis for these statements can be seen by expressing the Schild equation in logarithmic form ... 

A Schild plot (based on the results of a student class experiment on the effect of atropine on the contractile response of guinea-pig ileum to acetylcholine) is shown in Figure 1.17. Note that the line is straight, and its slope is close to unity, as Eq. (1.51) predicts. 

FIGURE 1.17 Schild plot for the action of atropine in antagonizing the action of acetylcholine on guinea-pig ileum. Each point gives the mean the standard error of the mean of the number of observations shown. 

Figure 1.21, like Figure 1.19, shows two Schild plots, one of which (open circles) departs greatly from the expected behavior. The deviation occurs when noradrenaline is the agonist and again it can be accounted for in terms of the reduction in local concentration caused by the uptake, process... 

FIGURE 1.21 Schild plots for the antagonism by propranolol of the actions of noradrenaline (open circles) and isoprenaline (closed circles) on the contractile force of the isolated atrium of the guinea pig. The x shows the value obtained with noradrenaline as agonist but in the presence of cocaine (20 pM). (From Furchgott, R. F., Handbook of Experimental Pharmacology, Vol. 23, 1972, pp. 283-335 based on the results of Blinks, J. R Ann. N.Y.Acad. Sci., 139, 673-685, 1967.)... 

Hence, a Schild plot based on the results of such an experiment will give an estimate not of KB but of Kb + [C]IKc). 

Here, Km and Km are the equilibrium constants for the blocker at the two sites. In this situation, the Schild plot is not linear it has a slope of less than unity at antagonist concentrations around Kb (where KB = (KB1KB2)m) and tends to unity at high or at low antagonist concentrations (Colquhoun, 1986). 

Utilizing the dose-ratio (relative potency) data that we obtained for GT-1 and GT-2, we constructed constrained Schild plots to obtain an estimation of the pA2 (= -log apparent affinity constant). An estimation of the p 2 values is indicated by the intercept of a best fit line of slope of -1 (Figure 5). 

P-ARK An enzyme that phosphoylates the occupied form of a G-protein coupled receptor, e.g. the 6-adrenoceptor, leading to uncoupling of that receptor and desensitization. ARMI age-related memory impairment, arrhythmia (dysrhythmia) An abnormality of heart rhythm or rate of heartbeat, usually caused by disturbance of the electrical impulses and their conduction within the heart. They include ectopic beats (isolated irregular beats), tachycardias (too fast a heartbeat), bradycardias (too slow a heartbeat) and atrial flutter and ventricular fibrillation. Arthus reaction A severe local inflammatory response, a skin reaction characterized by erythema, oedema, necrosis, local haemorrhage. A type III hypersensitivity reaction. Arunlakshana and Schild plot See Schild plot, ascites fluid The fluid that accumulates in the peritoneal cavity during certain pathological conditions, aspiration The withdrawal of fluid or tissue from the body by suction. 

Clark plot A graphical method of estimation of the affinity of a competitive antagonist from a linear plot of the Caddum-Schild equation. In practice, any advantages of this plot have been overlooked, and the logarithmic form of this equation is almost universally used in the Schild plot class The taxonomic group immediately ranking above the order and below the phylum. 

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