Acetylcholine

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Acetylcholine is a neurotransmitter used 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. It also plays an important role in regulating the inflammatory response.

Function[edit | edit source]

Acetylcholine is required for the generation of muscular force. In the central nervous system, acetylcholine modulates arousal and temperature regulation. It also may play a role in central fatigue. During exercise, levels of acetylcholine drop.[1]

Immune system[edit | edit source]

The vagus nerve speaks directly to the immune system via acetylcholine.[2][3][4]

Acetylcholine plays a role in innate immunity through nicotinic acetylcholine receptors and in the adaptive immune response via M3 muscarinic acetylcholine receptors (M3R).[5]

Muscarinic receptors[edit | edit source]

Knockout mice, that is mice lacking the gene that encodes for M3R, had impaired response to bacterial infection, while normal mice given a muscarinic agonist (to increase the activity of M3R) had enhanced production of IL-13 and IFN-γ.[6] Another study used a muscarinic agonist and an antagonist (reduce activity) and found that the antagonist suppressed the immune response while the agonist exaggerated it.[7]

Mast cells[edit | edit source]

Several studies suggest a relationship between autonomic nervous system dysfunction and mast cell activation via acetylcholine.

One study found that acetylcholine via muscarinic receptors strongly inhibited the release of histamine in mucosal mast cells.[8] The activity of acetylcholinesterase, the enzyme that breaks down acetylcholine, was found to be significantly increased in 64% of patients experiencing flares of ulcerative colitis.[9]

In human disease[edit | edit source]

Myasthenia Gravis[edit | edit source]

Autoantibodies to acetylcholine receptors, alpha subunit have been found in patients with myasthenia gravis. These cross react with herpesvirus glycoprotein D. [10] Antibodies to acetylcholine receptor and HSV-1 antigens crossreact.[11]

B cells from myasthenia gravis patient stimulated in vitro by Epstein-Barr virus produced acetylcholine autoantibodies.[12] Ongoing EBV infection of the thymus has been posited as a causative agent for the production of aceytlcholine receptor autoantibodies in myasthenia gravis.[13][14]

Sjögren Syndrome[edit | edit source]

Autoantibodies against muscarinic acetylcholine receptor on exocrine glands were found in patients with Sjögren Syndrome.[15]

Chronic fatigue syndrome[edit | edit source]

In 2015, a large German study found 29% of ME/CFS patients had elevated autoantibodies to M3 and M4 muscarinic acetylcholine receptors, as well as ß2 adrenergic receptors.[16] A 2016 Australian study found that ME/CFS patients had significantly greater numbers of single nucleotide polymorphisms associated with the gene encoding for M3 muscarinic acetylcholine receptors.[17]

Anecdotally, some ME/CFS patients have tried Mestinon, an aceytlcholinesterase inhibitor that increases circulating acetylcholine and is used to treat myasthenia gravis, with some success.[18] A work in progress study of exercise intolerance in preload failure found that Mestinon improved exercise tolerance, but the study has not yet been published.[19]

Postural orthostatic tachycardia[edit | edit source]

Learn more[edit | edit source]

See also[edit | edit source]

References[edit | edit source]

  1. Conlay, L. A., Sabournjian, L. A., and Wurtman, R. J. Exercise and neuromodulators: choline and acetylcholine in marathon runners.Int. J. Sports Med. 13(Suppl. 1):S141-142, 1992
  2. https://www.sciencedaily.com/releases/2007/10/071024083630.htm
  3. http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_24-2-2015-14-16-10
  4. http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004636
  5. http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004636
  6. http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004636
  7. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2323336/
  8. http://www.atsjournals.org/doi/full/10.1164/ajrccm.156.2.96-12079#.V7vo-ZMrLMV
  9. https://www.myknowtions.com/portfolio/autonomic-nervous-alterations-and-mast-cell-degranulation-in-the-exacerbation-of-ulcerative-colitis
  10. https://books.google.com/books?id=5trQOK8hcZUC&pg=PA7&lpg=PA7&dq=coxsackie+b+acetylcholine&source=bl&ots=zhup8ZXq68&sig=CxDwQCHO8-OMBYkcp4EayjnDKnw&hl=en&sa=X&ved=0ahUKEwjflpmqg9fOAhWBeSYKHSR4Dh0Q6AEIMTAD#v=onepage&q=coxsackie%20b%20acetylcholine&f=false
  11. http://www.ncbi.nlm.nih.gov/pubmed/10742556
  12. http://www.ncbi.nlm.nih.gov/pubmed/2553772
  13. http://www.academia.edu/20258853/Epstein-barr_virus_Trigger_for_autoimmunity/
  14. http://journals.lww.com/neurologynow/_layouts/15/oaks.journals.mobile/post.aspx?blogId=2&postId=10
  15. http://www.omicsonline.org/open-access/autoantibodies-against-muscarinic-acetylcholine-receptor-on-exocrine-glands-in-sjgren-syndrome-2161-1122.1000265.pdf
  16. http://www.meaction.net/2015/09/26/antibodies-found-in-subset-of-cfs-patients/
  17. http://www.la-press.com/examination-of-single-nucleotide-polymorphisms-in-acetylcholine-recept-article-a4862
  18. http://www.healthrising.org/blog/2016/06/17/mestinon-chronic-fatigue-vagus-nerve-stimulation-exercise/
  19. Oliveira, R.K. (2016). "Pyridostigmine for Exercise Intolerance Treatment in Preload Failure". American Journal of Respiratory and Critical Care Medicine. 


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From MEpedia, a crowd-sourced encyclopedia of ME and CFS science and history
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