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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Nyckelord

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

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)