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.
Skomedal
T
T
Department of Pharmacology, University of Oslo, Norway. lor.skomedal@labmed.uio.no
Fu
M L
ML
Hjalmarson
A
A
Hoebeke
J
J
Schiander
I G
IG
Osnes
J B
JB
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D000937:Antigen-Antibody Reactions / Q000187:drug effects; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D007074:Immunoglobulin G / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology*; D008969:Molecular Sequence Data; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D043585:Receptor, Muscarinic M2; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology; D011976:Receptors, Muscarinic / Q000276:immunology* / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D000906:Antibodies; D007074:Immunoglobulin G; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D010455:Peptides; D043585:Receptor, Muscarinic M2; D018342:Receptors, Adrenergic, beta-1; D011976:Receptors, Muscarinic; D001285:Atropine; D002217:Carbachol; D007545:Isoproterenol