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acetylcholine

acetylcholine is a neurotransmitter released from nerve endings (terminals) in both the peripheral and the central nervous systems. It is synthesized within the nerve terminal from choline, taken up from the tissue fluid into the nerve ending by a specialized transport mechanism. The enzyme necessary for this synthesis (choline acetyltransferase) is formed in the nerve cell body and passes down the axon to its end, carried in the axoplasmic flow, the slow movement of intracellular substance (cytoplasm). Acetylcholine is stored in the nerve terminal, sequestered in small vesicles awaiting release.

When a nerve action potential reaches and invades the nerve terminal, a shower of acetylcholine vesicles is released into the junction (synapse) between the nerve terminal and the ‘effector’ cell which the nerve activates. This may be another nerve cell or a muscle or gland cell. Thus electrical signals are converted to chemical signals, allowing messages to be passed between nerve cells or between nerve cells and non-nerve cells. This process is termed ‘chemical neurotransmission’ and was first demonstrated, for nerves to the heart, by the German pharmacologist Loewi in 1921. Chemical transmission involving acetylcholine is known as ‘cholinergic’.

Acetylcholine acts as a transmitter between motor nerves and the fibres of skeletal muscle at all neuromuscular junctions. At this type of synapse, the nerve terminal is closely apposed to the cell membrane of a muscle fibre at the so-called motor end plate. On release, acetylcholine acts almost instantly, to cause a sequence of chemical and physical events (starting with depolarization of the motor endplate) which cause contraction of the muscle fibre. This is exactly what is required for voluntary muscles in which a rapid response to a command is required. The action of acetylcholine is terminated rapidly, in around 10 milliseconds; an enzyme (cholinesterase) breaks the transmitter down into choline and an acetate ion. The choline is then available for re-uptake into the nerve terminal.

These same principles apply to cholinergic transmission at sites other than neuromuscular junctions, although the structure of the synapses differs. In the autonomic nervous system these include nerve-to-nerve synapses at the relay stations (ganglia) in both the sympathetic and the parasympathetic divisions, and the endings of parasympathetic nerve fibres on non-voluntary (smooth) muscle, the heart, and glandular cells; in response to activation of this nerve supply, smooth muscle contracts (notably in the gut), the frequency of heart beat is slowed, and glands secrete. Acetylcholine is also an important transmitter at many sites in the brain at nerve-to-nerve synapses.

To understand how acetylcholine brings about a variety of effects in different cells it is necessary to understand membrane receptors. In post-synaptic membranes (those of the cells on which the nerve fibres terminate) there are many different sorts of receptors and some are receptors for acetylcholine. These are protein molecules that react specifically with acetylcholine in a reversible fashion. It is the complex of receptor combined with acetylcholine which brings about a biophysical reaction, resulting in the response from the receptive cell. Two major types of acetylcholine receptors exist in the membranes of cells. The type in skeletal muscle is known as ‘nicotinic’; in glands, smooth muscle, and the heart they are ‘muscarinic’; and there are some of each type in the brain. These terms are used because nicotine mimics the action of acetylcholine at nicotinic receptors, whereas muscarine, an alkaloid from the mushroom Amanita muscaria, mimics the action of acetylcholine at the muscarinic receptors.

Alan W. Cuthbert


See also autonomic nervous system; neurotransmitters.

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Acetylcholine

Acetylcholine


Acetylcholine is the neurotransmitter produced by neurons referred to as cholinergic neurons. In the peripheral nervous system acetylcholine plays a role in skeletal muscle movement, as well as in the regulation of smooth muscle and cardiac muscle. In the central nervous system acetylcholine is believed to be involved in learning, memory, and mood.

Acetylcholine is synthesized from choline and acetyl coenzyme A through the action of the enzyme choline acetyltransferase and becomes packaged into membrane-bound vesicles . After the arrival of a nerve signal at the termination of an axon, the vesicles fuse with the cell membrane, causing the release of acetylcholine into the synaptic cleft . For the nerve signal to continue, acetylcholine must diffuse to another nearby neuron or muscle cell, where it will bind and activate a receptor protein.

There are two main types of cholinergic receptors, nicotinic and muscarinic. Nicotinic receptors are located at synapses between two neurons and at synapses between neurons and skeletal muscle cells. Upon activation a nicotinic receptor acts as a channel for the movement of ions into and out of the neuron, directly resulting in depolarization of the neuron. Muscarinic receptors, located at the synapses of nerves with smooth or cardiac muscle, trigger a chain of chemical events referred to as signal transduction.

For a cholinergic neuron to receive another impulse, acetylcholine must be released from the receptor to which it has bound. This will only happen if the concentration of acetylcholine in the synaptic cleft is very low. Low synaptic concentrations of acetylcholine can be maintained via a hydrolysis reaction catalyzed by the enzyme acetylcholinesterase. This enzyme hydrolyzes acetylcholine into acetic acid and choline. If acetylcholinesterase activity is inhibited, the synaptic concentration of acetylcholine will remain higher than normal. If this inhibition is irreversible, as in the case of exposure to many nerve gases and some pesticides, sweating, bronchial constriction, convulsions, paralysis, and possibly death can occur. Although irreversible inhibition is dangerous, beneficial effects may be derived from transient (reversible) inhibition. Drugs that inhibit acetylcholinesterase in a reversible manner have been shown to improve memory in some people with Alzheimer's disease.

see also Neurotransmitters.

Jennifer L. Powers

Bibliography

Whittaker, V. (1990). "The Contribution of Drugs and Toxins to Understanding of Cholinergic Function." Trends in Physiological Sciences 11:813.

Internet Resources

Basic Neuropharmacology. "The Chemistry of the Nervous System." Available from <http://www.ptd.neu.edu/neuroanatomy/cyberclass>.

King, Michael W. "Biochemistry of Neurotransmitters." Available from <http://web.indstate.edu/thcme/mwking>.

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acetylcholine

acetylcholine (əsēt´əlkō´lēn), a small organic molecule liberated at nerve endings as a neurotransmitter. It is particularly important in the stimulation of muscle tissue. The transmission of an impulse to the end of the nerve causes it to release neurotransmitter molecules onto the surface of the next cell, stimulating it. After such release, the acetylcholine is quickly broken into acetate and choline, which pass back to the first cell to be recycled into acetylcholine again. The poison curare acts by blocking the transmission of acetylcholine. Some nerve gases operate by preventing the breakdown of acetylcholine causing continual stimulation of the receptor cells, which leads to intense spasms of the muscles, including the heart. Acetylcholine is often abbreviated as Ach. See nervous system.

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Acetylcholine

ACETYLCHOLINE

Acetylcholine (ACh) is a major Neurotransmitter in the central and peripheral nervous systems. It is the ester of acetate and choline, formed by the enzyme choline acetyl transferase, from choline and acetyl-CoA. This was the first substance (ca. 1906) to meet the criteria of identification for a neurotransmitter. Later, acetylcholine was shown to be the general neurotransmitter for the neuromuscular junctions. In all vertebrate species, it is the major neurotransmitter for all autonomic ganglia and the neurotransmitter between parasympathetic ganglia and their target cells. Acetylcholine neurotransmission occurs widely within the central nervous system. Collections of Neurons arising within the brainthe medulla, the pons, or the anterior diencephaloninnervate a wide set of cortical and subcortical targets; some of these circuits are destroyed in Alzheimer's disease.

(See also: Scopolomine and Atropine )

BIBLIOGRAPHY

Cooper, J. R., Bloom, F. E., & Roth, R. H. (1996). The biochemical basis of neuropharmacology, 7th ed. New York: Oxford University Press.

Floyd Bloom

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acetylcholine

acetylcholine (ACh) One of the main neurotransmitters of the vertebrate nervous system. It is released at certain (cholinergic) nerve endings and may be excitatory or inhibitory; it initiates muscular contraction at neuromuscular junctions. Acetylcholine receptors (cholinoceptors) fall into two main classes: muscarinic and nicotinic receptors. Once acetylcholine has been released it has only a transitory effect because it is rapidly broken down by the enzyme cholinesterase.

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acetylcholine

acetylcholine (ACh) An acetyl ester of choline that is involved in synaptic (see SYNAPSE) transmission between nerve cells. It is released from vesicles by the presynaptic neurone and diffuses across the synaptic cleft where it interacts with specific receptors to produce a local depolarization of the postsynaptic membrane, thus enabling the transmission of nerve impulses.

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acetylcholine

a·ce·tyl·cho·line / əˌsētlˈkōˌlēn; ˌasitl-/ • n. Biochem. a compound that occurs throughout the nervous system, in which it functions as a neurotransmitter.

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acetylcholine

acetylcholine The acetyl derivative of choline, produced at cholinergic nerve endings both in the brain, where it acts as a chemical transmitter, and at the junctions between nerves and muscles, where it stimulates muscle contraction.

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acetylcholine

acetylcholine (ass-i-tyl-koh-leen) n. the acetic acid ester of the organic base choline: the neurotransmitter released at the synapses of parasympathetic nerves and at neuromuscular junctions. See also cholinesterase.

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