What is a Receptor?
It is a basic necessity of living things to respond to the environment and, to do this, they need to sense and react to their surroundings. At a single cell level, this is the function of receptors—proteins on the outside surface of a cell that signal what's happening around the cells and trigger a response.
Receptors actually bridge across the membrane that surrounds the cell so part of the receptor protein is on the outside and part on the inside. When a receptor interacts with something in the environment, like a chemical (i.e., a "ligand"), the part inside the cell responds by starting a chain reaction (technically a "signaling cascade") that causes the cell to do something such as make a hormone or perhaps send a signal if it is a nerve cell.
What are GPCRs?
The most common types of receptors all start the signal in the cell the same way. They make a change to a small chemical—a type of guanine nucleotide that's present in the cell. Like knocking over the first domino in a row, this chemical "switch" triggers a cascade that ends up making multiple adjustments to the biology of the cell, such as turning genes on or off, or clumping certain proteins together. Since the chemical switch is guanine, the protein that turns it on is called a G-Protein (G for guanine) and the receptors are G-Protein Coupled Receptors or "GPCRs."
GPCRs and Drug Development
So what makes GPCRs so interesting for drug development? It is simply that they happen to make ideal drug targets. They are right on the surface of cells so they are easy for drugs to interact with, and their primary role is to tell cells what's happening around them and get them to respond. If you want to get some type of cell to react in a certain way, such as stopping a pain signal, producing a chemical to make you sleepy, or turning out less of a certain type of cholesterol, there is a good chance you can find a GPCR to activate or block to make this happen.
Over a third of all current drugs target GPRCs, including Claritin, Prozac, Zoloft, Zantac, Allegra. Almost every pharmaceutical company spends millions each year looking for new chemicals that activating or block particular GPCRs and so might make good drugs. The receptors for taste, smell, hormones, even light are all GPCR proteins floating on the membranes of specific cells. At current count there are almost 800 different GPCRs.
How are Drugs that Affect GPCRs Found?
When a GPCR senses something and starts to signal, there are a couple types of chain reactions that propagate and amplify the signal in the cell. Generally, these are called secondary messengers and it is these chemicals in the cell that investigators searching for new GPCR drugs need to detect.
Some secondary messengers can be detected by simply adding certain types of fluorescent dyes to normal cells, but some require bioengineered cells with secondary messengers that have been modified to be detected with particular chemicals. In both cases, detection usually involves the production of some sort of fluorescent or luminescent chemical that can be measured on specialized instruments.
How Is GPCR Drug Screening Done?
Standard lab procedures are not really feasible for screening of large numbers of chemicals that activate GPCR proteins to find new drugs. GPCR assays need to be amenable to automated handling and signals need to be easily detected so that thousands of reactions can be run in a day.
Large-scale high-throughput screening is done in standardized plates with rows of small reaction wells where each chemical is tested. This type of research requires automated robotics to add the cells, aliquot chemicals and reagents, mix the reactions, and read the results. Lab automation is itself a large specialized industry segment that closely overlaps with biotechnology since it is mostly used in drug screening.