ANTI-M-2 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 M-2 receptors was studied in adult rat v entricular myocardium. These anti-muscarinic M-2 receptor antibodies s hifted the dose-response relationship of the beta-adrenoceptor agonist isoproterenol to higher concentrations whereas preimmune rabbit immun oglobulin G (IgG) or antibodies against the N-terminus of the beta(1)- adrenoceptor had no effect. This effect of anti-muscarinic M-2 recepto r antibodies was fully blocked after preincubation with the antigenic peptide. No significant change of maximal inotropic response to isopro terenol was observed in the presence of anti-muscarinic M-2 receptor a ntibodies. The anti-muscarinic M-2 receptor antibodies did apparently not hamper the access of the muscarinic receptor agonist carbachol. Th e muscarinic receptor antagonist atropine attenuated the effect of the anti-muscarinic M-2 receptor antibodies. The present study demonstrat es for the first time in intact adult ventricular myocardium a specifi c stimulatory muscarinic activity of antibodies raised against a part of the muscarinic M-2 receptor protein. (C) 1997 Elsevier Science B.V.