51 Acetylcholine (ACh)

Acetylcholine: neurotransmitter of muscles and the parasympathetic system, Alzheimer disease and myasthenia gravis.

Acetylcholine (ACh) is a neurotransmitter formed from choline and acetyl coenzyme A. It was the first neurotransmitter discovered; its role was shown by Otto Loewi in the 1920s. ACh transmits signals from motor nerves to skeletal muscles (the neuromuscular junction), in all autonomic ganglia, and from parasympathetic nerves to the heart, gut, bladder and glands. In the brain it supports attention, learning, memory and arousal. ACh acts on two types of receptors: nicotinic (muscles, ganglia, brain) and muscarinic (heart, smooth muscle, glands, brain). After release it is rapidly broken down by acetylcholinesterase.

NeurotransmittersNervous systemCholinergic system

Made fromcholine + acetyl-CoA

Receptorsnicotinic, muscarinic

Broken down byacetylcholinesterase

Blood levelnot a routine clinical test

Figure 1. Synthesis, action and breakdown of acetylcholine. ChAT = choline acetyltransferase.

Effects of acetylcholine

Muscles: contraction of skeletal muscle
Parasympathetic effects: slower heart rate, narrowing of the airways and more bronchial secretions, increased gut motility and secretions, bladder emptying, pupil constriction, salivation and sweating
Brain: attention, memory, learning, sleep–wake regulation

Clinical significance

Alzheimer disease: loss of cholinergic neurons contributes to memory decline; cholinesterase inhibitors (donepezil, rivastigmine, galantamine) increase ACh in the brain
Myasthenia gravis: autoantibodies against the ACh receptor or related proteins at the neuromuscular junction cause fatigable muscle weakness (drooping eyelids, double vision, difficulty swallowing); cholinesterase inhibitors and immunotherapy are used
Anticholinergic medicines (some antihistamines, antidepressants, bladder medicines) can cause dry mouth, constipation, urinary retention and confusion, especially in older people
Excess acetylcholine occurs in poisoning with organophosphates or nerve agents

Blood acetylcholine is not used in routine diagnosis because it is broken down within milliseconds; the cholinergic system is assessed through clinical signs, antibody tests and cholinesterase activity.

When to see a doctor

Progressive memory problems, or muscle weakness that worsens with activity (drooping eyelids, double vision, difficulty chewing or swallowing), need neurological assessment.

References

Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet. 2008;371(9612):597–607. doi:10.1016/S0140-6736(07)61202-1

This article is for general information and does not replace a consultation with a doctor. Laboratory results must be interpreted by a physician together with symptoms and other tests.

Published on 28 April 2024