A Novel Method to Estimate Levels of Receptors Using an Allosteric Modulator: Focus on Muscarinic M1 Receptor

This chapter outlines some of the general principles that need to be considered when developing a radioligand binding assay to measure the affinity and density of radioligand binding to a receptor in tissue or on cells. In addition it describes an innovative step forward in using radioligand binding assays to measure levels of muscarinic M1 receptors in human postmortem CNS, using both membrane binding and in situ radioligand binding. These examples show how, using receptor-specific allosteric modulators, it is possible to gain an estimate of the density of a single receptor using a radioligand that is not totally specific to the target site of interest. Given there is a growing understanding that there are problems with antibodies not showing specificity to their supposed target protein, well-characterized radioligand binding techniques still provide an important tool when studying receptor density in tissues and cells.