Urate binding to plasma proteins

In 1961 Gutman and Yu proposed a three component system for the regulation of the renal excretion of uric acid in man. The first component of this system is filtration of plasma urate at the glomerulus. While this process is certain to be operative in the human kidney, its quantitative role in the renal excretion of uric acid in man depends upon the extent of urate binding to plasma proteins in vivo. This is a subject that is being discussed in another section of this symposium and will not be considered further in this paper. The second and third component of this system relate to uric acid reabsorption and secretion by the human nephron. Ample data is available to document that both of these processes are operable in the human kidney (Gutman and Yu, 1957 Gutman, et al., 1959), but the relative contribution of each to the final excretion of uric acid has been difficult to determine with conventional clearance techniques. However, a potential solution to this problem of bidirectional uric acid transport appeared in 1967 when Steele and Rieselbach introduced the "pyrazinamide suppression test . 

CONTENTS OF VOLUME 41B Urate Binding to Plasma Proteins... 

By expressing drug concentrations as that required to displace 50 per cent of the baseline bound urate, the relative urate displacing capacities can be compared (Table IV). Aspirin is again the most potent urate displacer, probenecid the least. We have subsequently demonstrated a variety of agents which inhibit the binding of urate to plasma proteins and to date all such agents have been uricosuric. Other substances, such as bilirubin, have also been shown to interfere with the urate-plasma protein interaction. 

Glycopyrrolate did not appear to alter the binding of urate to plasma proteins as determined by the technique of equilibrium dialysis at 4 C (Fig. 5). 

Fig. 5. The binding of urate to plasma proteins at 4 C is plotted as a function of uric acid concentration in the dialyzing bath. A.B., control, glycopyrrolate, o. J.W., control, glycopyrrolate, . ...

The Binding of Urate to Plasma Proteins J. R. Klinenberg, R. Bluestone,... 

---