Acetylcholine (ACh) is an organic chemical that acts as a neurotransmitter in the brain and body of several animal types (including humans), a chemical message produced by nerve cells to send signals to other cells, such as neurons, muscle cells, and cells of the gland. Its name derives from its chemical structure: it is an acetic acid and choline ester. Sections of the body that use or are influenced by acetylcholine are considered cholinergic elements. Cholinergic and anticholinergics, respectively, are called substances that increase or decrease the overall cholinergic system function.
Not only the most common chemical messenger, but acetylcholine was also the very first neurotransmitter to be identified as well. It was discovered in 1914 by Henry Hallett Dale, and Otto Loewi later confirmed its existence. For their discovery, both individuals were awarded the 1936 Nobel Prize in Physiology/Medicine.
Acetylcholine is the parasympathetic nervous system's chief neurotransmitter, a component of the autonomic nervous system (a peripheral nervous system branch) that contracts smooth muscles, dilates blood vessels, increases body secretions, and slows the heart rate. A response can be stimulated or blocked by acetylcholine and thus can have excitatory or inhibitory effects.
Acetylcholine is processed at the ends of cholinergic neurons (producing acetylcholine) in vesicles. In the peripheral nervous system, acetylcholine is released into the neuromuscular junction when a nerve impulse arrives at the terminal of a motor neuron. There, it interacts with a receptor molecule in a muscle fiber’s postsynaptic membrane (or end-plate membrane). This binding alters the membrane permeability, opening up channels that allow positively charged sodium ions to flow into the muscle cell (see the end-plate potential).
Sodium channels along the end-plate membrane become fully regulated as successive nerve impulses accumulate at a sufficiently high frequency, resulting in the contraction of muscle cells.
Role of Acetylcholine
A variety of body functions, including the cardiovascular system, are influenced by its movements within the autonomic nervous system, where it serves as a vasodilator, decreases heart rate, and decreases heart muscle contraction.
It serves to increase peristalsis in the stomach and the amplitude of digestive contractions in the gastrointestinal system. Its operation reduces the bladder's capacity in the urinary tract and increases voluntary voiding pressure.
It also impacts the respiratory system and activates all glands receiving parasympathetic nerve impulses to secrete. Acetylcholine tends to have several functions in the central nervous system.
Acetylcholine acts in the brain as a neurotransmitter and as a neuromodulator. There are a variety of cholinergic areas in the brain, each with different roles, such as playing an important role in excitement, concentration, memory, and motivation.
It is believed to play a major role in memory and learning, and in the brain of people with Alzheimer's disease, it is in abnormally short supply.
Use of Acetylcholine in Medicine
In medicine, there are many uses to inhibit, hinder, or imitate the action of acetylcholine. Drugs that function on the acetylcholine system are either receptor agonists, activating the system, or inhibiting it with antagonists. The receptor agonists and antagonists of acetylcholine may either directly affect the receptors or indirectly exert their effects, e.g. by affecting the acetylcholinesterase enzyme that degrades the ligand-receptor. Agonists increase the activation level of the receptor, and antagonists decrease it.
Owing to its multifaceted activity (non-selective) and rapid inactivation by choline, acetylcholine itself does not have therapeutic value as a drug for intravenous administration.
However, during cataract surgery, it is used in the form of eye drops to induce constriction of the pupil, which encourages rapid post-operational recovery.
Disease and Disorders
Myasthenia gravis syndrome, characterized by muscle weakness and fatigue, occurs when the body improperly develops antibodies to the nicotinic receptors of acetylcholine and thereby prevents the proper transmission of acetylcholine signals. The motor end-plate is lost over time. Drugs that competitively inhibit acetylcholinesterase are successful in treating this condition (e.g., neostigmine, physostigmine, or especially pyridostigmine).
Do You Know?
Acetylcholine is synthesized from the compounds choline and acetyl-CoA by the enzyme choline acetyltransferase in some neurons. Cholinergic neurons have the capacity to generate ACh. An example of a central cholinergic area is the nucleus basalis of Meynert in the basal forebrain. The enzyme acetylcholinesterase converts acetylcholine into the inactive metabolites choline and acetate. In the synaptic cleft, this enzyme is abundant, and its role is important for proper muscle function in rapidly clearing free acetylcholine from the synapse. Some neurotoxins function by inhibiting acetylcholinesterase, thus leading to excess neuromuscular junction acetylcholine.