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Agonist-like activity of anti-peptide antibodies directed against an autoimmune epitope on the heart muscarinic acetylcholine receptor.

Artikel i vetenskaplig tidskrift
Författare Michael Fu
W Gerd
H Ake
H Johan
Publicerad i Receptors & channels
Volym 2
Nummer/häfte 2
Sidor 121-30
ISSN 1060-6823
Publiceringsår 1994
Publicerad vid Wallenberglaboratoriet
Sidor 121-30
Språk en
Länkar www.ncbi.nlm.nih.gov/entrez/query.f...
Ämnesord Adenylate Cyclase, metabolism, Amino Acid Sequence, Animals, Animals, Newborn, Antibodies, immunology, isolation & purification, pharmacology, CHO Cells, Cells, Cultured, Cricetinae, Epitopes, analysis, immunology, Guanylyl Imidodiphosphate, pharmacology, Heart Rate, drug effects, Heart Ventricles, Humans, Immunoblotting, Kinetics, Molecular Sequence Data, Myocardium, metabolism, Peptides, chemical synthesis, immunology, Quinuclidinyl Benzilate, metabolism, Rabbits, immunology, Rats, Rats, Wistar, Receptors, Muscarinic, immunology, physiology, Recombinant Proteins, agonists, immunology, metabolism, Transfection
Ämneskategorier Cell- och molekylärbiologi, Mikrobiologi inom det medicinska området

Sammanfattning

A synthetic peptide corresponding to amino acids 169-193 of the second extracellular loop of the M2 human muscarinic receptor was used to raise antibodies in rabbits. Affinity purified antibodies specifically recognized a major band with a molecular weight of about 80 kDa on the electrotransferred membrane proteins of both rat ventricles and chinese hamster ovary cells expressing recombinant muscarinic receptors. Incubation of these antibodies with rat myocardial membranes resulted not only in a decrease in the maximal binding capacity, but also in a decrease in receptor antagonist affinity. These antibodies could also mimic the effects of agonist stimulation as demonstrated by inhibition of isoproterenol-stimulated cAMP accumulation and by a negative chronotropic effect on cultured cardiomyocytes. These results suggest that the second extracellular loop of the M2 muscarinic receptor is an immunologically and functionally important domain with properties comparable to those found for autoantibodies against the same domain in idiopathic dilated cardiomyopathy. It strengthens the hypothesis that the second extracellular loop of the members of the superfamily of G-protein coupled membrane receptors could be the main immunogenic region responsible for a pathogenic autoimmune response.

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