ABSTRACT
In this chapter, we look at ways in which the binding of ligands to macromolecules can be directly investigated. Although most interest centers on the interaction of drugs and hormones with receptors, the approach taken here can be applied to any similar binding process-for example, the combination of drugs with ion channels or membrane transport systems. The binding of ligands, including drugs, to plasma proteins has been studied for more than 50 years, but the study of binding to the much smaller amounts of protein (e.g., receptors) in cell membranes is more recent, having become feasible only when suitable radioactively labeled ligands became available. The rst rigorous study of drug binding to receptors was that of Paton and Rang (1965), who investigated 3H-atropine binding to muscarinic receptors in smooth muscle. The use of radiolabeled or uorescently labeled drugs in binding studies is now common and for many pharmaceutical manufacturers forms an essential part of the screening process, providing a rapid means of determining the afnity of new drugs for a wide range of receptors. Labeling of drugs with radioisotopes or the introduction of uorescent tags is attractive because very small quantities, often as low as 1 fmol, can be readily and accurately measured.
