Skip to main content

Advertisement

Log in

Presynaptic Membrane Receptor in Human Brain

  • Original Article
  • Published:
Indian Journal of Clinical Biochemistry Aims and scope Submit manuscript

Abstract

Myasthenia gravis (MG) is an autoimmune disease that results from antibody mediated damage of Acetylcholine receptor (AChR) at the neuromuscular junction. The autoimmune character of MG and pathogenic role of AChR antibodies have been established by several workers i.e., the demonstration of anti-AChR antibodies in about 90 % of MG patients. It has been demonstrated that patients with MG also have antibodies against a second protein named presynaptic membrane receptor (PsmR), which is identified by utilizing β-Bgtx, a ligand which binds to PsmR. Using β-Bgtx Sepharose 4B affinity matrix, the PsmR was purified from different regions of human cadaver brain by affinity chromatography. Purified receptor was characterized both by biochemical and immunological procedures. PsmR purified from different regions of the brain shows a specific activity of 0.37 ± 0.01, 0.39 ± 0.02 and 0.43 ± 0.005 nM/ μg of protein in Parietal lobe, Occipital lobe and Frontal lobe respectively. The affinity purified PsmR from the brain of 87 and 68 kd (parietal lobe, occipital lobe and frontal lobe) shows immunoreactivity with myasthenic sera. These findings suggest that PsmR from brain is another antigen against which autoantibodies are developed in Myasthenia gravis patients. Upon treatment with various enzymes we concluded that PsmR from brain is a glycoprotein in which the immunoreactivity resides in the carbohydrate as well as the peptide epitopes. In conclusion the PsmR is another antigen against which autoantibodies are formed in different regions of brain. These can be used as a diagnostic tool for detecting antibodies in the sera or cerebrospinal fluid of MG patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Aarli JA, Lefvert AK, Tonder O. Thymoma-specific antibodies in sera from patients with myasthenia gravis demonstrated by indirect haemagglutination. J Neuroimmunol. 1981;1(4):421–7.

    Article  PubMed  CAS  Google Scholar 

  2. Brenner T, Abramsky O, Lisak RP, Zweiman B, Tarab-Hazdai R, Fuchs S. Radio-immunoassay of antibodies to acetylcholine receptor in serum of myasthenia gravis patients. Isr J Med Sci. 1978;14(9):986–9.

    PubMed  CAS  Google Scholar 

  3. Chang CE, Lee CY. Isolation of neurotoxins from the venom of Bungarus multicinctus and their modes of neuromuscular blocking action. Arch Pharmacodyn Ther. 1962;144:241–57.

    Google Scholar 

  4. Chaun-Zhen L. Anti-presynaptic membrane receptor antibodies in myasthenia gravis. J Neurol Sci. 1991;102:39–45.

    Article  Google Scholar 

  5. Clarke PBS, Reuben M. Release of (3H)noradrenaline from rat hippocampal synaptosomes by nicotine: mediation by different nicotinic receptor subtypes from striatal (3H)dopamine release. Br J Pharmacol. 1996;117:595–606.

    Article  PubMed  CAS  Google Scholar 

  6. Conti-Tronconi BM, Raftery MA. The nicotinic cholinergic receptor: correlation of molecular structure with functional properties. Ann Rev Biochem. 1982;51:491–530.

    Article  PubMed  CAS  Google Scholar 

  7. Decker MW, Brioni ID, Bannon AW, Arneric SP. Diversity of neuronal nicotinic acetylcholine receptors: lessons from behavior and implications for CNS therapeutics. Life Sci. 1995;56(8):545–70.

    Article  PubMed  CAS  Google Scholar 

  8. Drachman DB, Angus CW, Adams RN, Michelson JD, Hoffman GJ. Myasthenic antibodies cross-link acetylcholine receptors to accelerate degradation. N Engl J Med. 1978;298:1116–22.

    Article  PubMed  CAS  Google Scholar 

  9. Dwyer DS, Bradly RJ. Antibodies against nicotinic acetylcholine receptor in myasthenia gravis. Clin Exp Immunol. 1979;37(3):448–51.

    PubMed  CAS  Google Scholar 

  10. Fambrough DM, Drachman DB, Satyamurti S. Neuromuscular junction in myasthenia gravis: decreased acetylcholine receptors. Science. 1973;182(1 09):293–5.

    Article  PubMed  CAS  Google Scholar 

  11. Gottic C, Conti-Tronconi BM, Raftry MA. Mammalian muscle acetylcholine receptor. Purification and characterization. Biochemistry. 1982;21(13):3148–54.

    Article  Google Scholar 

  12. Hedqvist P, Moawad A. Presynaptic alpha- and beta-adrenoceptor medicated control of noradrenaline release in human oviduct. Acta Physiol Scand. 1975;95(4):494–6.

    Article  PubMed  CAS  Google Scholar 

  13. Hinman CL, Hudson RA, Burek CL, Goodlow G, Rauch HC. An enzyme-linked immunosorbent assay for antibody against acetylcholine receptor. J Neurosci Methods. 1983;9(2):141–55.

    Article  PubMed  CAS  Google Scholar 

  14. Hoch W, McConville J, Helms S, Newsom-Davis J, Melms A, Vincent A. Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat Med. 2001;7(3):365–8.

    Article  PubMed  CAS  Google Scholar 

  15. Jailkhani BL, Asthana D, Jaffery NF, Subbalaxmi B. Alpha bungarotoxin aggregates on iodination with chloramine T but not with iodogen. J Neurol Immunol. 1984;6:337–45.

    CAS  Google Scholar 

  16. Jailkhani BL, Asthana D, Jaffery NF, Subbalaxmi KB, Ahuja GK. Elisa for detection of IgG and IgM Ab’s to nAChR in MG. Ind J Med Res. 1986;83:187–95.

    CAS  Google Scholar 

  17. Jailkhani BL, Asthana D, Jaffery NF, Kumar R, Ahuja GK. A simplified ELISA for antireceptor antibodies in MG. J Immunol Meth. 1986;86:115–8.

    Article  CAS  Google Scholar 

  18. Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970;227(5259):680–5.

    Google Scholar 

  19. Lefvert AK, Bergstrom K. Acetylcholine receptor antibody in myasthenia gravis: purification and characterization. Scand J Immunol. 1978;8(96):525–33.

    Article  PubMed  CAS  Google Scholar 

  20. Lennon VA, Lindstorm LM, Seybold ME. Experimental autoimmune myasthenia gravis: cellular and humoral immune responses. Ann N Y Acad Sci. 1976;274:283–99.

    Google Scholar 

  21. Lindstorm JM. Autoimmune response to acetylcholine receptor. Adv Immunol. 1979;27:1–50.

    Article  Google Scholar 

  22. Lindstorm JM, Seybold ME, Lennon VA, Shithnigam S, Duane DD. Antibody to AChR in MG prevalance, clinical correlates and diagnostic value. Neurology. 1976;26:1054–9.

    Article  Google Scholar 

  23. Link H. Myasthenia gravis: T and B cell reactivities to the β-bungarotoxin binding protein presynaptic membrane receptor. J Neurol Sci. 1992;109:173–81.

    Article  PubMed  CAS  Google Scholar 

  24. Lowry OH, Rosenbrough NJ, Farra AL, Randall RJ. Protein measurement with Folin-phenol reagent. J Biol Chem. 1951;193(1):265–75.

    PubMed  CAS  Google Scholar 

  25. Lu CZ, Lu L, Hao ZS, Xia DG, Qain J, Arnason BG. Antibody-secreting cells to acetylcholine receptor and to presynaptic membrane receptor in seronegative myasthenia gravis. J Neuroimmunol. 1993;43(1–2):145–9.

    Article  PubMed  CAS  Google Scholar 

  26. Patrick J, Lindstorm J. Autoimmune response to acetylcholine receptor. Science. 1973;180(88):871–2.

    Article  PubMed  CAS  Google Scholar 

  27. Pestronk A. Intracellular acetylcholine receptor in skeletal muscle of adult rat. J Neurosci. 1985;5(5):1111–7.

    Google Scholar 

  28. Qiao J. β-Bungarotoxin binding protein is immunogenic but lacks myasthogenicity in rats. J Neurol Sci. 1994;121:190–3.

    Article  PubMed  CAS  Google Scholar 

  29. Rasool S, Jailkhani BL, Irshad M, Behari M, Suhail S, Shabirul H. Purification of beta bungarotoxin (β-Bgtx) binding protein from human cadaver skeletal muscle. J Med Sci. 2007;7:195–202.

    Article  CAS  Google Scholar 

  30. Rasool S, Behari M, Irshad M, Goyal V, Jailkhani BL. Antibodies against postsynaptic acetylcholine receptor and presynaptic membrane receptor in myasthenia gravis. Trends Med Res. 2008;3:64–71.

    Article  Google Scholar 

  31. Sanders DB, Howard JF Jr. Disorders of neuromuscular transmission. In: Bradley WG, Daroff RB, Fenichel GM, et al., editors. Neurology in clinical practice, the neurological disorders. Philadelphia: Butterworth Heinemann; 2004. p. 2441–61.

    Google Scholar 

  32. Schmidt RR, Betz H. The β-Bgtx binding protein from chicken brain biding sites for different neuronal K+ channel ligands co-factors upon partial purification. FEBS Lett. 1988;340:65–70.

    Article  Google Scholar 

  33. Skeie O, Romi F, Aarli JA, et al. Pathogenesis of myositis and myasthenia associated with titin and ryanodine receptor antibodies. Ann N Y Acad Sci. 2003;998:343–50.

    Article  PubMed  CAS  Google Scholar 

  34. Somnier FE, Engel PJ. The occurrence of anti-titin antibodies and thymomas: a population survey of MG 1970–1999. Neurology. 2002;59:92–8.

    Article  PubMed  Google Scholar 

  35. Toyka KV, Drachman DB, Griffin DE, Pestronk A, Winkelstein JA, Fishbeck KH, et al. Myasthenia gravis. Study of humoral immune mechanisms by passive transfer to mice. N Engl J Med. 1977;296(3):125–31.

    Article  PubMed  CAS  Google Scholar 

  36. Vincent A, Leite MI. Neuromuscular junction autoimmune disease: muscle specific kinase antibodies and treatments for myasthenia gravis. Curr Opin Neurol. 2005;18(5):519–25.

    Article  PubMed  CAS  Google Scholar 

  37. Vincent A, Newsom-Davis J. Alpha-bungarotoxin and anti-acetylcholine receptor antibody binding to human acetylcholine receptor. In: Ceccarelli B, Clementi F, editors. Advance’s in cytopharmacology. Neurotoxins-tools in neurobiology, vol. 3. New York: Raven; 1979. p. 267–78.

    Google Scholar 

  38. Vincent A, Newsome D. Acetylcholine receptor antibody as a diagnostic test for MG. J Neuro Neurosurg Psychiatry. 1985;48:1246–52.

    Article  CAS  Google Scholar 

  39. Wiedenmann B, Franke WW. Identification and localization of synaptophysin, an integral membrane glycoprotein of Mr 38,000 characteristic of presynaptic vesicles. Cell. 1985;41(3):1017–28.

    Article  PubMed  CAS  Google Scholar 

  40. Xiao B-G. Immunological specificity and cross reactivity of anti-acetylcholine receptor and anti-presynaptic membrane receptor antibodies in myasthenia gravis. J Neurol Sci. 1991;105:118–23.

    Article  PubMed  CAS  Google Scholar 

  41. Yi Q, Pirskanen R, Lefvert AK. Presynaptic membrane receptor-reactive T lymphocytes in myasthenia gravis. Scand J Immunol. 1996;43(1):81–7.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Suhail Rasool.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rasool, S., Behari, M., Goyal, V. et al. Presynaptic Membrane Receptor in Human Brain. Ind J Clin Biochem 28, 124–135 (2013). https://doi.org/10.1007/s12291-012-0248-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12291-012-0248-1

Keywords

Navigation