Serum Albumin Binding of Natural Substances and Its Influence on the Biological Activity of Endogenous and Synthetic Ligands for G-Protein-Coupled Receptors
Serum albumin is one of the most abundant blood plasma proteins and is produced in the liver. Apart from its role in maintenance of oncotic pressure, it serves as a carrier for many endogenous molecules, including steroid hormones, hemin and fatty acids. In addition, it is capable of binding a wide array of natural substances. Several of these are helpful in the treatment of hypertension and hypercholesterolemia or useful as antioxidants. Related to this, the first part of this chapter deals with the serum albumin binding to polyphenols. In the next part, we will discuss the ability of serum albumin to modulate the binding of endogenous and synthetic ligands to G-protein-coupled receptors. Serum albumin is not only a binder for these ligands but is also capable of modulating the potency of endogenous ligands to activate these receptors. In the examples discussed in this chapter, it appears that the potency of angiotensin II and cholecystokinin-8 to activate their respective receptors is enhanced in the presence of bovine serum albumin (BSA). On the other hand, BSA acts as a functional antagonist to profoundly reduce the potency of α-linolenic acid to activate its cognate free fatty acid type 1 receptors. Based on these divergent effects, an accurate determination of ligand-receptor activation in the presence of serum albumin contributes to the understanding of the potency of natural, endogenous and synthetic ligands.