Antibodies against astrocyte M1 and M2 muscarinic cholinoceptor from schizophrenic patients' sera.
We demonstrated the presence of circulating antibodies from schizophrenic patients able to interact with cultured astrocytes activating muscarinic acetylcholine receptors (mAChRs). Sera and purified IgG from 15 paranoid schizophrenic and 15 age-matched normal subjects were studied by indirect immunofluorescence (IFI), flow cytometry, dot blot, enzyme immunoassay (ELISA), and radioligand competition assays. Astrocyte membranes and/or a synthetic peptide, with identical amino acid sequence of human M(1) and M(2) mAChR, were used as antigens. By IFI and flow cytometry procedures, we proved that serum purified IgG fraction from schizophrenic patients, reacted to astrocyte cell surface. The same antibodies were able to inhibit the binding of the specific mAChR radioligand (3)H-QNB. Using synthetic peptide for dot blot and ELISA, we demonstrated that these antibodies reacted against the second extracellular loop of human cerebral M(1) and M(2) mAChR. Also, the corresponding affinity-purified antipeptide antibody displayed an agonistic-like activity associated to specific M(1) and M(2) mAChR activation, increasing inositol phosphates accumulation and decreasing cyclic AMP production, respectively. This article gives support to the participation of an autoimmune process in schizophrenia disease.
Borda
Tania
T
Pharmacology Unit, School of Dentistry, University of Buenos Aires, Marcelo T. de Alvear 2142, piso 4 to. Sector B, 1122AAH Buenos Aires, Argentina.
Gomez
Ricardo
R
Berría
Maria I
MI
Sterin-Borda
Leonor
L
D000109:Acetylcholine / Q000378:metabolism; D000328:Adult; D000818:Animals; D000918:Antibody Specificity; D001253:Astrocytes / Q000276:immunology* / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood* / Q000302:isolation & purification; D001667:Binding, Competitive / Q000187:drug effects / Q000276:immunology; D001921:Brain / Q000276:immunology* / Q000503:physiopathology; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D043643:Receptor, Muscarinic M1 / Q000276:immunology*; D043585:Receptor, Muscarinic M2 / Q000276:immunology* / Q000378:metabolism; D012559:Schizophrenia / Q000097:blood* / Q000276:immunology* / Q000503:physiopathology; D009435:Synaptic Transmission / Q000276:immunology
D001323:Autoantibodies; D007074:Immunoglobulin G; D007295:Inositol Phosphates; D018727:Muscarinic Antagonists; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D000242:Cyclic AMP; D000109:Acetylcholine