Acetylcholine

Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals, and humans, as a neurotransmitter—a chemical message released by nerve cells to send signals to other cells . Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Parts in the body that use or are affected by acetylcholine are referred to as cholinergic. Substances that interfere with acetylcholine activity are called anticholinergics. Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals, and humans, as a neurotransmitter—a chemical message released by nerve cells to send signals to other cells . Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Parts in the body that use or are affected by acetylcholine are referred to as cholinergic. Substances that interfere with acetylcholine activity are called anticholinergics. Acetylcholine is the neurotransmitter used at the neuromuscular junction—in other words, it is the chemical that motor neurons of the nervous system release in order to activate muscles. This property means that drugs that affect cholinergic systems can have very dangerous effects ranging from paralysis to convulsions. Acetylcholine is also a neurotransmitter in the autonomic nervous system, both as an internal transmitter for the sympathetic nervous system and as the final product released by the parasympathetic nervous system. Acetylcholine is the primary neurotransmitter of the parasympathetic nervous systems. Acetylcholine (ACh), has also been traced in cells of non-neural origins and microbes. Recently, enzymes related to its synthesis, degradation and cellular uptake have been traced back to early origins of unicellular eukaryotes. The protist pathogen Acanthamoeba spp. has shown the presence of ACh, which provides growth and proliferative signals via a membrane located M1-muscarinic receptor homolog. In the brain, acetylcholine functions as a neurotransmitter and as a neuromodulator. The brain contains a number of cholinergic areas, each with distinct functions; such as playing an important role in arousal, attention, memory and motivation. Partly because of its muscle-activating function, but also because of its functions in the autonomic nervous system and brain, a large number of important drugs exert their effects by altering cholinergic transmission. Numerous venoms and toxins produced by plants, animals, and bacteria, as well as chemical nerve agents such as Sarin, cause harm by inactivating or hyperactivating muscles via their influences on the neuromuscular junction. Drugs that act on muscarinic acetylcholine receptors, such as atropine, can be poisonous in large quantities, but in smaller doses they are commonly used to treat certain heart conditions and eye problems. Scopolamine, which acts mainly on muscarinic receptors in the brain, can cause delirium and amnesia. The addictive qualities of nicotine are derived from its effects on nicotinic acetylcholine receptors in the brain. Acetylcholine is a choline molecule that has been acetylated at the oxygen atom. Because of the presence of a highly polar, charged ammonium group, acetylcholine does not penetrate lipid membranes. Because of this, when the drug is introduced externally, it remains in the extracellular space and does not pass through the blood–brain barrier. A synonym of this drug is miochol. Acetylcholine is synthesized in certain neurons by the enzyme choline acetyltransferase from the compounds choline and acetyl-CoA. Cholinergic neurons are capable of producing 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. This enzyme is abundant in the synaptic cleft, and its role in rapidly clearing free acetylcholine from the synapse is essential for proper muscle function. Certain neurotoxins work by inhibiting acetylcholinesterase, thus leading to excess acetylcholine at the neuromuscular junction, causing paralysis of the muscles needed for breathing and stopping the beating of the heart. Acetylcholine functions in both the central nervous system (CNS) and the peripheral nervous system (PNS). In the CNS, cholinergic projections from the basal forebrain to the cerebral cortex and hippocampus support the cognitive functions of those target areas. In the PNS, acetylcholine activates muscles and is a major neurotransmitter in the autonomic nervous system. Like many other biologically active substances, acetylcholine exerts its effects by binding to and activating receptors located on the surface of cells. There are two main classes of acetylcholine receptor, nicotinic and muscarinic. They are named for chemicals that can selectively activate each type of receptor without activating the other: muscarine is a compound found in the mushroom Amanita muscaria; nicotine is found in tobacco. Nicotinic acetylcholine receptors are ligand-gated ion channels permeable to sodium, potassium, and calcium ions. In other words, they are ion channels embedded in cell membranes, capable of switching from a closed to an open state when acetylcholine binds to them; in the open state they allow ions to pass through. Nicotinic receptors come in two main types, known as muscle-type and neuronal-type. The muscle-type can be selectively blocked by curare, the neuronal-type by hexamethonium. The main location of muscle-type receptors is on muscle cells, as described in more detail below. Neuronal-type receptors are located in autonomic ganglia (both sympathetic and parasympathetic), and in the central nervous system.