These cells respond by increasing production of nitric oxide , which signals the surrounding smooth muscle to relax, leading to vasodilation. In the central nervous system, ACh has a variety of effects on plasticity, arousal and reward. ACh has an important role in the enhancement of alertness when we wake up,  in sustaining attention  and in learning and memory. Damage to the cholinergic acetylcholine-producing system in the brain has been shown to be associated with the memory deficits associated with Alzheimer's disease.
In the brainstem acetylcholine originates from the Pedunculopontine nucleus and laterodorsal tegmental nucleus collectively known as the meso pontine tegmentum area or pontomesencephalotegmental complex. In addition, ACh acts as an important internal transmitter in the striatum , which is part of the basal ganglia. It is released by cholinergic interneurons. In humans, non-human primates and rodents, these interneurons respond to salient environmental stimuli with responses that are temporally aligned with the responses of dopaminergic neurons of the substantia nigra.
Acetylcholine has been implicated in learning and memory in several ways.
Complete morphologies of basal forebrain cholinergic neurons in the mouse
The anticholinergic drug, scopolamine , impairs acquisition of new information in humans  and animals. The disease myasthenia gravis , characterized by muscle weakness and fatigue, occurs when the body inappropriately produces antibodies against acetylcholine nicotinic receptors, and thus inhibits proper acetylcholine signal transmission. Over time, the motor end plate is destroyed. Drugs that competitively inhibit acetylcholinesterase e.
Complete morphologies of basal forebrain cholinergic neurons in the mouse | eLife
They allow endogenously released acetylcholine more time to interact with its respective receptor before being inactivated by acetylcholinesterase in the synaptic cleft the space between nerve and muscle. Blocking, hindering or mimicking the action of acetylcholine has many uses in medicine. Drugs acting on the acetylcholine system are either agonists to the receptors, stimulating the system, or antagonists, inhibiting it.
Acetylcholine receptor agonists and antagonists can either have an effect directly on the receptors or exert their effects indirectly, e. Agonists increase the level of receptor activation, antagonists reduce it. Acetylcholine itself does not have therapeutic value as a drug for intravenous administration because of its multi-faceted action non-selective and rapid inactivation by cholinesterase.
However, it is used in the form of eye drops to cause constriction of the pupil during cataract surgery, which facilitates quick post-operational recovery. Nicotine binds to and activates nicotinic acetylcholine receptors , mimicking the effect of acetylcholine at these receptors. This causes a depolarization, and results in an excitatory post-synaptic potential. Thus, ACh is excitatory on skeletal muscle; the electrical response is fast and short-lived. Curares are arrow poisons, which act at nicotinic receptors and have been used to develop clinically useful therapies.
Many ACh receptor agonists work indirectly by inhibiting the enzyme acetylcholinesterase. The resulting accumulation of acetylcholine causes continuous stimulation of the muscles, glands, and central nervous system, which can result in fatal convulsions if the dose is high. They are examples of enzyme inhibitors , and increase the action of acetylcholine by delaying its degradation; some have been used as nerve agents Sarin and VX nerve gas or pesticides organophosphates and the carbamates.
Many toxins and venoms produced by plants and animals also contain cholinesterase inhibitors. In clinical use, they are administered in low doses to reverse the action of muscle relaxants , to treat myasthenia gravis , and to treat symptoms of Alzheimer's disease rivastigmine , which increases cholinergic activity in the brain.
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Organic mercurial compounds, such as methylmercury , have a high affinity for sulfhydryl groups , which causes dysfunction of the enzyme choline acetyltransferase. This inhibition may lead to acetylcholine deficiency, and can have consequences on motor function. Botulinum toxin Botox acts by suppressing the release of acetylcholine, whereas the venom from a black widow spider alpha-latrotoxin has the reverse effect.
ACh inhibition causes paralysis. When bitten by a black widow spider , one experiences the wastage of ACh supplies and the muscles begin to contract. If and when the supply is depleted, paralysis occurs. Acetylcholine is used by organisms in all domains of life for a variety of purposes. It is believed that choline, a precursor to acetylcholine, was used by single celled organisms billions of years ago for synthesizing cell membrane phospholipids. Acetylcholine is used by bacteria, fungi, and a variety of other animals. Many of the uses of acetylcholine rely on its action on ion channels via GPCRs like membrane proteins.
The two major types of acetylcholine receptors, muscarinic and nicotinic receptors, have convergently evolved to be responsive to acetylcholine. This means that rather than having evolved from a common homolog, these receptors evolved from separate receptor families. It is estimated that the nicotinic receptor family dates back longer than 2. Both of these receptor groups have evolved numerous subtypes with unique ligand affinities and signaling mechanisms.
The diversity of the receptor types enables acetylcholine to creating varying responses depending on which receptor types are activated, and allow for acetylcholine to dynamically regulate physiological processes. Acetylcholine ACh was first identified in by Henry Hallett Dale for its actions on heart tissue. It was confirmed as a neurotransmitter by Otto Loewi , who initially gave it the name Vagusstoff because it was released from the vagus nerve.
Both received the Nobel Prize in Physiology or Medicine for their work. Acetylcholine was also the first neurotransmitter to be identified. From Wikipedia, the free encyclopedia. Not to be confused with Acetyl chloride. This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.
IUPAC name. Main article: Acetylcholine receptor. Main article: Neuromuscular junction. Main article: Nicotinic receptor. Main article: Muscarinic receptor. Main article: Cholinesterase inhibitors. Asian Pacific Journal of Tropical Disease. Lott; Elizabeth B. June 4, ACS Chem Neurosci. Signal Transduct. Nutritional and Herbal Therapies for Children and Adolescents. Front Syst Neurosci.
Functional Aspects of the Basal Forebrain Cholinergic System
Miller's Anesthesia 7th ed. Elsevier Health Sciences. Trends Pharmacol. Brain Res Cogn Brain Res. Brain Res. Projections from the pontomesencephalic tegmentum to the thalamus, tectum, basal ganglia, and basal forebrain". Descending projections of the pontomesencephalic tegmentum".
Aust N Z J Psychiatry. Black dots represent cell body location and the vertical bar represents the mediolateral extent of the axon arbor.