Acetylcholine (ACh) is the most important and most abundant neurotransmitter in the human body. It serves as the primary neurotransmitter between neurons and muscles.

Structure and Form:
The chemical formula for acetylcholine is C7H16NO21+. It is rarely referred to as anything other than acetylcholine. Generally, acetylcholine is synthesized as acetylcholine chloride, C7H16NO2Cl.

Synthesis:
In the body, choline and acetyl coenzyme A (acetyl-CoA) combine in the presence of choline acetyltransferase (ChAT) yielding acetylcholine and coenzyme A in equilibrium. Or, in other words,

Choline + Acetyl coenzyme A <-(Choline Acetyltransferase)-> Acetylcholine + coenzyme A.
The choline comes from either dietary choline or phosphatidylcholine. Cholines are usually abundant in the body since they form the basis of fat. Acetyl coenzyme A is a product of metabolism through Kreb's cycle. Cholinergic neurons produce the synthetic enzyme choline acetyltransferase which allows the combination to occur.

Metabolism:
Acetylcholine is broken down to its components by either acetylcholinesterase (AChE), cholinesterase (ChE), or other nonspecific esterases.

Mechanism:
Once generated by cholinergic neurons, acetylcholine finds and activates acetylcholine receptors produced by cholinoceptive cells. There are two types of cholinoceptive cells: those that generate nicotinic receptors and those that generate muscarinic receptors.

Nicotinic acetylcholine receptors are found in mainly in skeletal muscle but also in other areas of the central nervous system. Nicotine is a potent agonist, causing the same effects as acetylcholine. This type of receptor contributes greatly to nicotine addiction as areas of the hypothalamus that control motivation have high concentrations of these receptors.

Muscarinic acetylcholine receptors are prevalent in smooth muscle, glands, the central nervous system, and most importantly, the heart. For these receptors, muscarine is a potent agonist.

Neurotransmitters are complex biological systems. Consequently, receptor agonists and antagonists will be not be treated here. They deserve their own nodes.

Effects:
In the human body, acetylcholine makes the bronchi and gut contract, stimulates saliva and mucus production and controls skeletal muscle. This neurotransmitter is also associated with memory function in the brain. Recent research links a shortage of acetylcholine with Alzheimer's disease.

Acetylcholinesterase Inhibitors:
The level of acetylcholine can be increased by inhibiting the enzyme that breaks it down. This category of drugs include: prescription pharmaceuticals such as Tacrine and Galantamine, herbal extracts such as Huperzine A, and nerve agents such as Soman. For the most part, these acetylcholinesterase inhibitors are used to treat Alzheimer's disease.

History:
In 1903 Otto Loewi wondered why different nerves control the heart in different ways as a response to the same electrical pulse. He came up with a hypothesis that the two nerves of the heart in question (i.e. the vagus nerve and the accelerator nerve) released different chemicals when stimulated. However, this hypothesis was neither tested nor proven until much later.

Loewi identified acetylcholine as vagusschtuff (German for vagus substance) in 1921. He dissected a frog and placed its heart in saline solution. While the heart continued to beat, he attached electrodes to the vagus nerve and stimulated it. The resulting solution was applied to another similarly situated heart and caused that heart to slow. This conclusively proves that it was a chemical that causes the change in the heart. Eventually Loewi received the 1936 Nobel Prize in Medicine for this discovery.

Sources:
http://members.aol.com/Bio50/LecNotes/lecnot00c.html
http://www.mult-sclerosis.org/acetylcholine.html
http://www.raysahelian.com/acetylch.html
http://www.gerd.com/intro/noframe/arp.htm
http://www.ptd.neu.edu/neuroanatomy/cyberclass/pharmacology/acetylcholine.htm
http://www.neurosci.pharm.utoledo.edu/MBC3320/acetylcholine.htm
http://www.ptd.neu.edu/neuroanatomy/cyberclass/pharmacology/AchReceptors.htm
Principles of Medicinal Chemistry. Foye, W.O., T.L. Lemke and D.A. Williams. Williams & Wilkins. Fourth Edition, 1995.
The RBI Handbook of Receptor Classification and Signal Transduction. K.J. Watling. RBI. Third Edition, 1998.

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