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

Artikel i vetenskaplig tidskrift
Författare T Skomedal
Michael Fu
Åke Hjalmarson
Johan Hoebeke
I G Schiander
J B Osnes
Publicerad i European journal of pharmacology
Volym 333
Nummer/häfte 2-3
Sidor 169-75
ISSN 0014-2999
Publiceringsår 1997
Publicerad vid Wallenberglaboratoriet
Hjärt-kärlinstitutionen
Institutionen för invärtesmedicin
Sidor 169-75
Språk en
Länkar www.ncbi.nlm.nih.gov/entrez/query.f...
Ämnesord 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
Ämneskategorier Fysiologi

Sammanfattning

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.

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