G protein-coupled receptor (GPCR) (GPCR)

G protein-coupled receptors (GPCRs) are the largest family of membrane proteins in the human genome, characterized by seven transmembrane alpha-helices that bridge the extracellular and intracellular environments (StatPearls, NBK551511). They function as molecular switches, transducing extracellular signals—including hormones, neurotransmitters, and light—into intracellular responses by activating heterotrimeric G proteins (Nature Reviews Drug Discovery, nrd.2017.178). This signaling regulates a vast array of physiological processes such as heart rate, immune response, and sensory perception. Because of their critical roles in physiology and their accessibility on the cell surface, GPCRs are the targets of approximately 34% of all FDA-approved drugs (NIH, PMC4156803). Drugs interacting with these receptors can act as agonists to stimulate signaling or antagonists to block it, providing a versatile means of therapeutic intervention. Pathological GPCR signaling is implicated in numerous conditions, ranging from hypertension and diabetes to various forms of cancer and neurological disorders. Therapeutic challenges include achieving subtype selectivity to avoid off-target effects and managing receptor desensitization or tolerance over time.

Other names

7-transmembrane domain receptor7TM receptorHeptahelical receptorSerpentine receptorG protein-linked receptor

Drugs targeting GPCRs typically act as agonists, antagonists, or inverse agonists to modulate the receptor's conformational state, thereby either initiating or inhibiting the activation of associated heterotrimeric G proteins and downstream second messenger cascades like cAMP or calcium signaling (StatPearls, NBK551511; Nature Reviews Drug Discovery, nrd.2017.178).