| Acetylcholine |
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| CATEGORIES ABOUT ACETYLCHOLINE | |
| choline esters | |
| acetates | |
| neurotransmitters | |
| quaternary ammonium compounds | |
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The Chemical Compound acetylcholine, often abbreviated as '''ACh''', was the first Neurotransmitter to be identified. It is a chemical transmitter in both the Peripheral Nervous System (PNS) and Central Nervous System (CNS) in many organisms including Humans . CHEMISTRY Acetylcholine is an Ester of Acetic Acid and Choline with Chemical Formula CH3CO O CH2 CH2 N +( CH3 )3. This structure is reflected in the systematic name, ''2-( Acetyl Oxy )- N,N,N - Tri Methyl Ethan Aminium ''. Acetylcholine (ACh) was first identified in 1914 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 1936 Nobel Prize In Physiology Or Medicine for their work. Later work showed that acetylcholine binding to Acetylcholine Receptor s on striated Muscle fibers, opened channels in the membrane. Sodium ions then enter the muscle cell, stimulating muscle contraction. Acetylcholine is also used in the Brain , where it tends to cause excitatory actions. The Gland s that receive impulses from the parasympathetic part of the Autonomic Nervous System are also stimulated in the same way. Acetylcholine is synthesized in certain Neuron s by the Enzyme Choline Acetyltransferase from the compounds Choline and Acetyl-CoA . Organic mercurial compounds have a high affinity for sulfhydryl groups, which attributes to its effect on enzyme dysfunction of choline acetyl transferase. This inhibition may lead to acetylcholine deficiency, and can have consequences on motor function. Normally, the enzyme Acetylcholinesterase converts acetylcholine into the inactive metabolites choline and Acetate . The devastating effects of Nerve Agent s are due to their inhibition of this enzyme, resulting in continuous stimulation of the muscles, glands and central nervous system. Certain insecticides are effective because they inhibit this enzyme in insects. On the other hand, since a shortage of acetylcholine in the Brain has been associated with Alzheimer's Disease , some drugs that inhibit acetylcholinesterase are used in the treatment of that disease. RELEASE SITES Acetylcholine is released by:
Botulin acts by suppressing the release of acetylcholine; where the venom from a Black Widow Spider has the reverse effect. PHARMACOLOGY There are two main classes of acetylcholine receptor (AChR), nicotinic and muscarinic. They are named for the ligands used to discover the receptors. Nicotinic AChRs are Ionotropic Receptors permeable to Sodium , Potassium , and Chloride ions. They are stimulated by Nicotine and blocked by Curare . All peripheral AChRs are nicotinic, such as those on the heart or at the neuromuscular junction. They are also found in wide distribution through the brain, but in relatively low numbers. Muscarinic receptors are Metabotropic and affect neurons over a longer time frame. They are stimulated by Muscarine , and blocked by Atropine , which is the poison found in the Belladonna plant. Extracts from the plant included this compound, and its action on muscarinic AChRs that increased pupil size was used for attractiveness in many European cultures in the past. Now, ACh is sometimes used during Cataract surgery to produce rapid constriction of the pupil. It must be administered intraocularly because Corneal Cholinesterase metabolizes topically administered ACh before it can diffuse into the eye. It is sold by the trade name Miochol-E (CIBA Vision). Similar drugs are used to induce Mydriasis (dilation of the pupil) in Cardiopulmonary Resuscitation and many other situations. The disease Myasthenia Gravis , characterized by muscle weakness and fatigue, occurs when the body inappropriately produces Antibodies against acetylcholine receptors, and thus inhibits proper acetylcholine signal transmission. Drugs that competitively inhibit acetylcholinesterase (e.g., neostigmine or physostigmine) are effective in treating this disorder. Blocking, hindering or mimicking the action of acetylcholine has many uses in medicine. Cholinesterase Inhibitor s increase the action of acetylcholine by delaying its degradation; some have been used as Nerve Agent s or Pesticide s. Clinically they are used to reverse the action of Muscle Relaxant s, to treat Myasthenia Gravis and in Alzheimer's Disease ( Rivastigmine , which increases cholinergic activity in the brain). ACh Receptor Agonists ACh Receptor Antagonists SOURCES
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