Impairment of agonist-induced M muscarinic receptor activation by autoantibodies from chagasic patients with cardiovascular dysautonomia.

Previous studies showed that circulating autoantibodies against M muscarinic receptors (anti-MR Ab) are associated with decreased cardiac parasympathetic modulation in patients with chronic Chagas disease (CD). Here we investigated whether the exposure of MR to such antibodies could impair agonist-induced receptor activation, leading to the inhibition of associated signaling pathways. Preincubation of MR-expressing HEK 293T cells with serum IgG fractions from chagasic patients with cardiovascular dysautonomia, followed by the addition of carbachol, resulted in the attenuation of agonist-induced G protein activation and arrestin-2 recruitment.