The most drugged receptor of all
A huge share of all medicines act on the G protein–coupled receptor (GPCR) family — receptors that thread through the membrane seven times and, on the inside, are wired to a G protein. Beta-blockers, opioids, antihistamines and many others all work here. Understanding the G protein switch therefore unlocks a large slice of pharmacology at once.
A G protein sits just inside the membrane, idle, holding a molecule called GDP (the 'off' fuel). When an agonist activates the receptor, the receptor nudges the G protein to swap GDP for GTP — and GTP is the 'on' state. The activated G protein then breaks away to switch its target enzyme or channel on or off. After a moment it quietly converts the GTP back to GDP and resets itself. It is, almost literally, a spring-loaded switch.
- At rest the G protein holds GDP and stays quiet, docked near the receptor.
- An agonist binds the receptor, which prods the G protein to exchange GDP for GTP — the 'on' signal.
- The active G protein detaches and travels to its effector enzyme or channel.
- The G protein slowly hydrolyses GTP back to GDP, turning itself off and ending the signal.
Three families, three personalities
Not all G proteins do the same thing. Three families cover most of what drugs care about. Gs stimulates the enzyme adenylyl cyclase, raising the messenger cAMP — think 'go faster'. Gi inhibits the same enzyme, lowering cAMP — think 'slow down'. Gq takes a different route entirely, activating phospholipase C to release calcium-mobilising messengers.
The same chemical can pull in opposite directions depending on which G protein its receptor uses. Adrenaline on a Gs-linked receptor speeds the heart; on a Gi-linked receptor elsewhere it can relax. This is why one drug, one receptor subtype, and one G protein must be considered together — and why the next guides follow the cAMP and calcium branches in detail.