The life cycle of acetylcholine
Acetylcholine is a small, fragile messenger with a short, busy life. Inside the nerve ending it is built from choline and an acetyl group, packed into tiny storage bubbles, and then dumped into the synapse when the nerve fires. It diffuses across, finds its receptor, delivers its message — and within milliseconds is chopped in half by an enzyme so the signal stops cleanly. Every cholinergic drug works by interfering with one of these steps.
synthesis: choline + acetyl-CoA --[choline acetyltransferase]--> acetylcholine storage: acetylcholine packed into vesicles release: nerve fires -> Ca2+ enters -> vesicles dump ACh into synapse action: ACh binds muscarinic (slow, GPCR) or nicotinic (fast, ion channel) termination: ACh --[acetylcholinesterase]--> choline + acetate (signal off)
Two receptors, two personalities
Acetylcholine talks to two completely different receptor families — a clear example of a receptor subtype split that matters enormously for drugs. The muscarinic receptor is a GPCR: it works slowly, through second messengers, and sits on the organs driven by the parasympathetic system — heart, glands, smooth muscle, eye. The nicotinic receptor is a ligand-gated ion channel: it works in milliseconds, and sits at autonomic ganglia and at the skeletal muscle endplate.
What muscarinic activation actually does
Switching on muscarinic receptors produces the classic rest-and-digest picture. A useful mnemonic is DUMBELS or simply: the body becomes wet and slow. Glands pour out fluid (tears, saliva, sweat, bronchial mucus), the gut and bladder contract, the pupil constricts, and the heart slows. Knowing this one paragraph lets you predict the effect — and the toxicity — of every drug that mimics or blocks muscarinic signalling in the rest of this track.
- Eyes: pupil constricts (miosis), near vision sharpens — the lens accommodates.
- Glands: tears, saliva, sweat, and airway mucus all increase.
- Heart: rate slows (bradycardia); airways narrow (bronchoconstriction).
- Gut and bladder: muscle contracts, moving contents along — more motility, more voiding.