G Protein-Coupled Receptor

A G protein-coupled receptor (GPCR) is a cell surface receptor protein that traverses the cell membrane 7 times and, when a ligand (signaling molecule) binds to it, activates an associated G protein on the inside of the cell. Activation of the G protein in turn triggers an intracellular signaling cascade (often involving production of second messengers like cAMP).

• GPCRs are also known as <u>seven-transmembrane receptors</u> because they have seven spanning helices in the membrane.
• Ligand binding causes the GPCR to undergo a conformational change that activates a <u>heterotrimeric G protein</u> (by causing the G protein's alpha subunit to exchange GDP for GTP). The G protein can then activate or inhibit downstream effectors (enzymes or ion channels), leading to changes in second messenger levels (e.g., increased cAMP).
• Example: <u>Adrenergic receptors</u> (for adrenaline/epinephrine) are GPCRs - when epinephrine binds, the GPCR activates a G protein that stimulates adenylyl cyclase to raise cAMP, triggering the fight-or-flight response.

• Clue in question stem: if it mentions a receptor with <u>7 transmembrane domains</u> that initiates a cascade via GTP-binding proteins and second messengers -> that's a G protein-coupled receptor.
• Term trap -> Ionotropic vs Metabotropic: GPCRs (like muscarinic acetylcholine receptors) are <u>metabotropic</u> (act through metabolic cascades), whereas ligand-gated ion channels (like nicotinic ACh receptors) are <u>ionotropic</u> (direct ion flow). Exams may test this distinction.
• Many drugs target GPCR pathways. For example, a question might mention beta-blockers working on beta-adrenergic receptors (a type of GPCR) - you'd be expected to recognize that these medications exert effects by blocking a GPCR-mediated signaling pathway.