ANTIPEPTIDE ANTIBODIES AGAINST AN AUTOIMMUNE EPITOPE ON HUMAN MUSCARINIC RECEPTOR MIMIC FUNCTIONAL AUTOANTIBODIES AGAINST THE SAME EPITOPE IN PATIENTS WITH IDIOPATHIC DILATED CARDIOMYOPATHY

A synthetic peptide corresponding to the sequence 169-193 of the secon d extracellular loop of the the human muscarinic receptor-2 was used t o mise antibodies in rabbits. Affinity-purified antibodies were able t o interface with muscarinic receptor radioligand binding and to recogn ize the muscarinic receptor protein in rats. The antibodies could also exert the physiological effects of muscarinic agonist stimulation as demonstrated by decreases in isoproterenol-stimulated cAMP accumulatio n in Guinea-pig ventricles heart beating frequency in cultured meonata l cardiomyocytes, the maximal rate of rise of ventricular pressure and heart rate in rats in-vivo. These results demonstrate that the second extracellular loop of the muscarinic acetylcholine receptor-2 is an i mmunologically and functionally important domain and that rabbit antib odies have properties comparable to those found for autoantibodies aga inst the same epitope in patients with idiopathic dilated cardiomyopat hy.