beta(1)-Adrenoceptor antibodies induce positive inotropic response in isolated cardiomyocytes.

• beta(1)-Adrenoceptor autoantibodies are present in approximately 30% of patients suffering from dilated cardiomyopathy. The inotropic effects mediated by these antibodies remain to be studied. Monoclonal antibodies were raised against a peptide corresponding to the second extracellular loop of the human beta(1)-adrenoceptor in balb/C mouse (n=6), and were characterized by enzyme immunoassay after purification by protein A. Purified immunoglobulin G from non-immunized animals (controls) did not influence Ca(2+) transient and cell shortening of rat cardiomyocytes measured by confocal-laser-scanning-microscopy. beta(1)-adrenoceptor antibodies caused a dose-related increase in Ca(2+) transient (dilution 1:2: +35.3+/-5.1%), and in cell shortening (dilution 1:2: +40.5+/-6.3%) (P<0.01 vs. controls). The effect of the beta(1)-adrenoceptor antibodies was blocked by the antigenic peptide and by the antagonist metoprolol. In addition, beta(1)-adrenoceptor antibodies induced a dose-dependent increase of the cyclic adenosine monophosphate. The inotropic response induced by isoproterenol was attenuated by the beta(1)-adrenoceptor antibody. beta(1)-adrenoceptor antibodies as partial agonists induce a specific positive inotropic effect via the protein-kinase-A-cascade.

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)

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

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Nyckelord

Adrenergic beta-Agonists

pharmacology

Adrenergic beta-Antagonists

pharmacology

Animals

Antibodies

Monoclonal

immunology

pharmacology

Cell Size

drug effects

Cells

Cultured

Cyclic AMP

analogs & derivatives

pharmacology

Dose-Response Relationship

Drug

Heart

drug effects

physiology

Humans

Isoproterenol

pharmacology

Metoprolol

pharmacology

Mice

Mice

Inbred BALB C

Myocardial Contraction

drug effects

Myocardium

cytology

metabolism

Propanolamines

pharmacology

Rats

Receptors

Adrenergic

beta-1

chemistry

immunology

Thionucleotides

pharmacology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)