03.02.1 Receptors

One of the most important targets for drug binding is receptors. These were originally known as specific receptive substance, which is a good description of what they do, they are specific receptive substance for individual endogenous compounds. Over the years, this has been shortened to receptors. There are receptors for many endogenous compounds, including hormones (endocrine and local), neurotransmitters, and growth factors. Each receptor is specific for one endogenous compound, which is also known as the endogenous regulatory ligand, with endogenous meaning contained within body/physiological, and ligand meaning a naturally occurring substance that binds to receptor.

Drugs that bind to receptors are either agonists or antagonists. Agonists usually mimic the effect of the endogenous ligand. In contrast, antagonists usually prevent the effect of the endogenous ligand. There are two main types of receptors. The first involves G-protein-coupled receptor (GPCR) signaling, and these are cell surface receptors that cross the cell membrane. Endogenous substance binds to the receptor on the outside of the cell to cause a change inside the cell, which is the first step in the cell signaling leading to an effect. GPCR signaling happens quickly (second/minutes), and is over quickly. For an ongoing effect, repeated stimulation of the receptor is needed.

The second type of receptors is receptors regulating nuclear transcription. To reach nuclear receptors, the endogenous compound must be able to cross the cell membrane. With nuclear receptors, the endogenous regulatory ligand binds to intracellular receptors, and the combination moves to the nucleus, and activates the first step in cell signaling leading to production of proteins. Protein synthesis requires some time, so this type of receptor activation is slower, and has a longer time course. Examples of these receptor types are discussed next.