G protein-coupled receptors (GPCRs) are a large group of proteins embedded in the cell membrane that allow a cell to respond to its environment. When a molecule, such as a hormone or neurotransmitter, binds to the outside of a receptor, it changes the receptor’s shape. This change initiates a signal cascade inside the cell, translating an external message into an internal action. The human genome encodes for approximately 800 different GPCRs, each specialized to recognize specific external signals.
GPCRs in Sensory Perception
Our perception of the world is highly dependent on G protein-coupled receptors. In vision, a GPCR called rhodopsin, located in the rod cells of the eye’s retina, detects light. When a photon of light strikes a rhodopsin molecule, it causes a chemical change in a bound molecule called retinal. This alters the shape of the rhodopsin protein, initiating a signaling cascade that leads to a nerve impulse being sent to the brain. This system allows for vision in dim light conditions.
The sense of smell, or olfaction, relies on a vast array of GPCRs known as olfactory receptors, found on the surface of sensory neurons in the nasal cavity. Humans have around 350 different types of these receptors, each capable of binding to specific odorant molecules. When an odor molecule binds to its corresponding receptor, it triggers a signal that is sent to the brain. The brain then integrates signals from multiple receptors to distinguish between thousands of distinct smells.
Taste, or gustation, also utilizes GPCRs to detect chemical compounds in food. The sensations of sweet, umami (savory), and bitter are mediated by these receptors on taste receptor cells within our taste buds. There are two main types of taste GPCRs: TAS1R and TAS2R. The TAS1R family detects sweet and umami tastes, while the TAS2R family, with about 30 different receptors, detects a wide variety of bitter compounds.
GPCRs in Regulating Body Functions
G protein-coupled receptors are also part of the body’s internal communication and regulation, including the hormonal response through adrenergic receptors. These receptors bind to the hormone adrenaline (epinephrine), initiating the “fight-or-flight” response. When adrenaline binds to adrenergic receptors in heart muscle, it leads to an increased heart rate and stronger contractions. In other tissues, this binding can trigger the breakdown of glycogen into glucose, mobilizing energy for immediate use.
In the brain, GPCRs are involved in neurotransmission, the process by which nerve cells communicate. Dopamine receptors are a class of GPCRs that play a part in mood, motivation, and the brain’s reward system. When the neurotransmitter dopamine binds to these receptors, it influences feelings of pleasure, focus, and satisfaction. Dysregulation of this system has been connected to several neurological conditions.
GPCRs as Pharmaceutical Targets
The involvement of GPCRs in a wide range of physiological processes makes them a focus for developing new medicines. An estimated 30-40% of all prescription drugs on the market work by targeting GPCRs. By designing molecules that can either activate or block these receptors, scientists can modulate cellular signaling to treat diseases. The diversity of GPCRs provides opportunities for creating specific therapies.
A common class of medications that target GPCRs are beta-blockers. These drugs work by blocking the action of adrenaline at beta-adrenergic receptors, a type of GPCR. By preventing adrenaline from binding, beta-blockers can help lower blood pressure, slow a rapid heart rate, and are used to treat cardiovascular conditions like hypertension and heart failure.
Another example of drugs targeting GPCRs is antihistamines. These medications relieve allergy symptoms such as sneezing, itching, and runny nose by blocking histamine receptors, another type of GPCR. When allergens cause immune cells to release histamine, it binds to its receptors to produce an inflammatory response. Antihistamines compete with histamine for these receptors, preventing it from binding and thereby reducing the allergic reaction.