Anti-M2 muscarinic receptor antibodies inhibit beta-adrenoceptor-mediated inotropic response in rat myocardium.

• The modulation of the inotropic effect by affinity-purified antibodies against a synthetic peptide corresponding to the second extracellular loop of the human muscarinic M2 receptors was studied in adult rat ventricular myocardium. These anti-muscarinic M2 receptor antibodies shifted the dose-response relationship of the beta-adrenoceptor agonist isoproterenol to higher concentrations whereas preimmune rabbit immunoglobulin G (IgG) or antibodies against the N-terminus of the beta 1-adrenoceptor had no effect. This effect of anti-muscarinic M2 receptor antibodies was fully blocked after preincubation with the antigenic peptide. No significant change of maximal inotropic response to isoproterenol was observed in the presence of anti-muscarinic M2 receptor antibodies. The anti-muscarinic M2 receptor antibodies did apparently not hamper the access of the muscarinic receptor agonist carbachol. The muscarinic receptor antagonist atropine attenuated the effect of the anti-muscarinic M2 receptor antibodies. The present study demonstrates for the first time in intact adult ventricular myocardium a specific stimulatory muscarinic activity of antibodies raised against a part of the muscarinic M2 receptor protein.

Subject headings

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

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

Keyword

Adrenergic beta-Agonists

pharmacology

Amino Acid Sequence

Animals

Antibodies

pharmacology

Antigen-Antibody Reactions

drug effects

Atropine

pharmacology

Carbachol

pharmacology

Dose-Response Relationship

Drug

Heart

drug effects

Immunoglobulin G

pharmacology

Isoproterenol

pharmacology

Molecular Sequence Data

Muscarinic Agonists

pharmacology

Muscarinic Antagonists

pharmacology

Myocardial Contraction

drug effects

Peptides

pharmacology

Rats

Receptor

Muscarinic M2

Receptors

Adrenergic

beta-1

immunology

Receptors

Muscarinic

immunology

metabolism

Publication and Content Type

ref (subject category)

art (subject category)