ABSTRACT
Endogenous ligand or synthetic agonist binding to specific cytokine, growth factor, hormone and neurotransmitter receptors is the first step in a complex signal transduction pathway which ultimately leads to the generation of defined physiological responses. Signaling pathways typically involve several different signal transduction molecules and are generally shared by structurally related receptors. In contrast to agonist binding, antagonist binding to receptors does not activate the receptor signal transduction pathway and, therefore, antagonists do not cause a cellular response. However, an antagonist will block the response of the endogenous agonist ligand. Although radioligand binding assay provides information concerning ligand binding to a receptor, this type of assay does not provide information concerning whether the receptor ligand is an agonist or antagonist. Assays are available which involve measurement of some aspects of receptor-mediated activation of the receptor signal transduction pathway and thus can serve as functional assays that can be used to distinguish receptor agonists and antagonists. Functional receptor assays are rapidly replacing radioligand binding assays as these assays become cheaper and simpler to perform. One of the primary reasons that functional receptor assays are becoming more popular as primary screening assays is that they have been simplified and are configured into a 96-well microtiter plate format for high throughput screening of a large numbers of extracts. The following section details several functional receptor assays that may be used as primary screens for screening combinatorial chemistry reaction products and natural product extracts.
