GM1 (monosialotetrahexosylganglioside) the "prototype" ganglioside, is a member of the ganglio series of gangliosides which contain one sialic acid residue. GM1 has important physiological properties and impacts neuronal plasticity and repair mechanisms, and the release of neurotrophins in the brain. Besides its function in the physiology of the brain, GM1 acts as the site of binding for both Cholera toxin and E. coli heat-labile enterotoxin (Traveller's diarrhea).[1][2]
Antibodies to GM1 are increased in Guillain-Barré syndrome, dementia and lupus but their function is not clear.[3] There is some evidence to suggest these antibodies are associated with diarrhoea in Guillain-Barré syndrome.[4]
GM1 and the cholera toxin
The bacteria Vibrio cholerae produces a multimeric toxin called the cholera toxin. The A1 subunit of this toxin will gain entry to intestinal epithelial cells via the GM1 ganglioside receptor. Once inside, the A1 subunit will ADP ribosylate the Gs Alpha subunit which will prevent its GTPase activity. This will lock it in the active state and it will continuously stimulate adenylate cyclase. The sustained adenylate cyclase activity will lead to a sustained increase of cAMP which will cause electrolyte and water loss, causing diarrhea.[citation needed]
Fortunately, the SGLT1 receptor is present in the small intestine. When the cholera patient is given a solution containing water, sodium and glucose, the SGLT1 receptor will reabsorb sodium and glucose, while water will be passively absorbed with the sodium. This will replace the water and electrolyte loss in the cholera induced diarrhea.
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References
- ^ Mocchetti I (2005). "Exogenous gangliosides, neuronal plasticity and repair, and the neurotrophins". Cell. Mol. Life Sci. 62 (19-20): 2283–94. doi:10.1007/s00018-005-5188-y. PMID 16158191.
- ^ Chen JC, Chang YS, Wu SL, et al. (September 2007). "Inhibition of Escherichia coli heat-labile enterotoxin-induced diarrhea by Chaenomeles speciosa". J Ethnopharmacol 113 (2): 233–9. doi:10.1016/j.jep.2007.05.031. PMID 17624704.
- ^ Bansal AS, Abdul-Karim B, Malik RA, et al. (1994). "IgM ganglioside GM1 antibodies in patients with autoimmune disease or neuropathy, and controls". J. Clin. Pathol. 47 (4): 300–2. doi:10.1136/jcp.47.4.300. PMID 8027366.
- ^ Irie S, Saito T, Kanazawa N, et al. (1997). "Relationships between anti-ganglioside antibodies and clinical characteristics of Guillain-Barré syndrome". Intern. Med. 36 (9): 607–12. doi:10.2169/internalmedicine.36.607. PMID 9313102.
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