Acetylcholine (ACh)

What is acetylcholine (ACh)?

Acetylcholine (ACh) is a neurotransmitter, a chemical that carries messages from your brain to your body through nerve cells. It’s an excitatory neurotransmitter. This means it “excites” the nerve cell and causes it to “fire off the message.”

Acetylcholine gets its name from the two substances that it’s made from — an acetyl group (acetyl coenzyme A, which comes from the sugar molecule glucose) and the nutrient choline. Choline is naturally present in foods, including egg yolks, soy, liver, seeds of vegetables and legumes. Choline is also made in your liver.

Acetylcholine is involved in many important functions in your body. It plays a major role in voluntary muscle movement all over your body. This is muscle movement you control. Nerve cells stimulate muscle nerve cells, causing muscles to contract. It also plays an important role in brain nerve cells, in such processes as memory, thinking and learning.

How is acetylcholine (ACh) made?

An enzyme called choline acetyltransferase causes a reaction between choline and the acetyl group to create acetylcholine. It’s made at the end of nerve cells.

How does acetylcholine (ACh) work?

Acetylcholine is stored at the end of nerve cells until it’s triggered to be released. Once released from the end of the nerve cell, it moves into a space called the synaptic cleft. The synaptic cleft is between the nerve cell from which acetylcholine was released (the presynaptic nerve cell) and the next nerve cell acetylcholine is going to (the postsynaptic nerve cell).

Once acetylcholine moves across the synapse, it can bind to two types of receptors: nicotinic receptors and muscarinic receptors. There are two subtypes of nicotinic receptors and five types of muscarinic receptors. After binding to the receptors, the chemical message moves along to the next nerve cell and then the process repeats until the message arrives at its destination.

Acetylcholine in the synapse is broken down by an enzyme called acetylcholinesterase into choline and acetate. These products are reabsorbed and recycled so they can be used again in transmitting another chemical message.

What does acetylcholine (ACh) do?

Acetylcholine has many roles.

When it binds to muscarinic receptors, it:

• Regulates heart contractions and blood pressure and decreases heart rate.
• Moves food through your intestine by contracting intestinal muscles and increasing stomach and intestine secretions.
• Causes glands to secrete substances such as tears, saliva, milk, sweat and digestive juices.
• Controls the release of urine.
• Contracts muscles that control near vision.
• Causes an erection.

When it binds to nicotinic receptors, it:

• Allows skeletal muscle to contract.
• Causes the release of adrenaline and norepinephrine from your adrenal glands.
• Activates your sympathetic system with the release of norepinephrine.

Both types of receptors are involved in memory, including long-term and working memory, memory formation and consolidation and retrieval.

Within your brain, acetylcholine is also involved in motivation, arousal, attention, learning and promoting rapid eye movement (REM) sleep.

Where is acetylcholine (ACh) found?

Acetylcholine is found in your central nervous system (CNS), your brain and spinal cord, as well as in your peripheral nervous system (the nerves that branch out from your CNS and connect with all other parts of your body, including muscles and organs).

Where does acetylcholine (ACh) work?

Acetylcholine is released both in your central nervous system (CNS), your brain and spinal cord, as well as in your peripheral nervous system (the nerves that branch out from your CNS and connect with all other parts of your body, including muscles and organs).

In your brain, acetylcholine originates from two major places: the basal forebrain and the mesopontine tegmentum area.

In your peripheral nervous system, acetylcholine is released into the neuromuscular junction. This is where nerves meet muscle cells.

Acetylcholine also plays a significant role in your autonomic nervous system, a branch of your peripheral nervous system. Your autonomic nervous system regulates many of the automatic functions of your body, such as the proper functioning of your internal organs.

Acetylcholine is also involved in your immune system and is secreted by T lymphocytes. T lymphocytes are a type of body-protective white blood cell.

What medical conditions are associated with low levels of acetylcholine (ACh)?

Low levels (deficiency) of acetylcholine play an important role in several diseases, the most common being:

• Alzheimer’s disease. People who have Alzheimer’s disease don’t have enough acetylcholine in their brains.
• Lambert-Eaton myasthenic syndrome. This disorder is caused by a reduction in the release of acetylcholine from nerve cells.
• Myasthenia gravis. This is an autoimmune disorder in which there’s a rapid weakening of skeletal muscles after repeated use. Some of the body’s antibodies interfere with acetylcholine receptors at the neuromuscular junction.

What other substances interrupt acetylcholine (ACh)?

Unfortunately, knowledge of how acetylcholine works in the body has been used to cause harm.

Nerve gases, such as sarin, and pesticides inhibit acetylcholinesterase, the enzyme that breaks down acetylcholine. A buildup of acetylcholine in the synapse paralyzes muscles, which can lead to death.

One type of spider causes harm to humans in a unique way. The venom from the bite of a black widow spider dramatically raises the acetylcholine level causing severe muscle contractions, spasms, paralysis and possible death.

What medications target acetylcholine (ACh)?

Cholinesterase inhibitors increase activity at acetylcholine receptors by blocking the breakdown of acetylcholine by the enzyme acetylcholinesterase. The result of blocking this enzyme is that there’s a buildup of acetylcholine in the synapse and continuous activation of the cholinergic receptors.

Cholinesterase inhibitors are used to treat Alzheimer’s disease and myasthenia gravis. In both of these conditions, there’s a severe decrease in the amount of acetylcholine receptor stimulation. Cholinesterase inhibitors, including donepezil (Aricept®), rivastigmine (Exelon®) and galantamine (Razadyne®), increase cholinergic transmission by inhibiting cholinesterase at the synapse. This action provides modest symptomatic benefits in some people with dementia.

Botulinum toxin — used to treat muscle spasticity, cosmetic wrinkles and migraines — works by preventing acetylcholine release from the end of nerve cells.

Is an acetylcholine (ACh) supplement available?

An acetylcholine dietary supplement isn’t available. However, supplements that increase acetylcholine release or that stop the breakdown of acetylcholine are thought to increase acetylcholine levels. One such supplement that increases acetylcholine release is choline. Supplements that stop the breakdown of acetylcholine include Bacopa monnieri, Ginkgo biloba and huperzine A.

Researchers say that more studies are needed to determine if dietary supplements improve memory and brain function, mental health conditions, including depression and bipolar disorder, and fetal growth and brain development.

Always talk with a healthcare provider before taking dietary supplements. They’ll offer advice about the benefits or lack of benefits of supplements and let you know if they’re known to interfere with medications you may be taking.

Is acetylcholine (ACh) present in food?

Choline, which is converted into acetylcholine, is found in many foods, including:

• Beef liver.
• Eggs.
• Beef top round.
• Roasted soybeans, canned kidney beans.
• Roasted chicken breast.
• Cod.
• Cooked quinoa.
• Cooked shiitake mushrooms, boiled broccoli and Brussels sprouts.
• Milk (1%), nonfat vanilla yogurt.

A note from Cleveland Clinic

Acetylcholine (ACh) is an important neurotransmitter that plays a role in brain functions, such as memory, and body functions, such as muscle contractions to move your muscles. Low levels of acetylcholine are associated with memory issues and muscle disorders. Cholinesterase inhibitors are used to treat Alzheimer’s disease and myasthenia gravis. The benefits of a choline supplement have yet to be fully determined.