Probing the immunological properties of the extracellular domains of the human beta(1)-adrenoceptor.

Mobini, Reza,1965Gothenburg University,Göteborgs universitet,Hjärt-kärlinstitutionen,Cardiovascular Institute (författare)

The human beta(1)-adrenoceptor is an immune target for autoantibodies with functional activity in cardiovascular diseases. Different epitopes on the extracellular domains of the receptor are involved. To study the immunological and pharmacological properties of these epitopes, rabbits were immunized with peptides corresponding to a large domain in the N-terminal part of the receptor and to its first and second extracellular loops. In contrast to the two other peptides, the first extracellular loop did not have immunogenic properties but acted as a hapten. Antibodies affinity-purified with the three synthetic peptides were able to significantly immunoprecipitate the solubilized receptor, confirming that they recognized the target receptor. While antibodies against the N-terminal domain did not inhibit the binding of a radiolabelled antagonist to the receptor, those against the first and second extracellular loop showed non-competitive inhibition. Similarly, only the two latter antibodies exerted a specific agonist-like effect on the receptor, as assessed on neonatal rat cardiomyocytes in culture. Our results are in accordance with those found for human anti-receptor autoantibodies with functional effects. We conclude that not all extracellular epitopes give rise to functional autoantibodies with potential physiopathological relevance in cardiac diseases with an autoimmune component.

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
Adrenergic beta-Agonists
Amino Acid Sequence
Animals
Animals
Newborn
Antibody Specificity
Autoantibodies
Cardiovascular Diseases
etiology
immunology
Cell Polarity
Cells
Cultured
Humans
Models
Molecular
Molecular Sequence Data
Myocardial Contraction
drug effects
Myocardium
cytology
Peptide Fragments
immunology
Rats
Receptors
Adrenergic
beta-1
immunology
T-Lymphocytes
immunology

Magnusson, Yvonne,1957Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory(Swepub:gu)xmagyv (författare)
Wallukat, G (författare)
Viguier, M (författare)
Hjalmarson, Agneta,1943 (författare)
Hoebeke, Johan (författare)
Göteborgs universitetHjärt-kärlinstitutionen (creator_code:org_t)

Av författaren/redakt...: Mobini, Reza, 19 ...; Magnusson, Yvonn ...; Wallukat, G; Viguier, M; Hjalmarson, Agne ...; Hoebeke, Johan

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Mikrobiologi ino ...

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