BACKGROUND AND AIMS Gastrointestinal disorders is one of the clinical manifestations of chronic Chagas' disease. The pathogenesis seems to be associated with autonomic dysfunction. Here, we consider the muscarinic cholinoceptor mediated alteration in distal colon function in chagasic megacolon.

PATIENTS Patients were divided into four groups: group I, chronic chagasic patients with megacolon; group II, chronic chagasic patients without megacolon; group III, non-chagasic patients with megacolon; and group IV, normal healthy volunteers (control).

RESULTS Group I but not the other groups had circulating antibodies capable of interacting with human colon activating M₂ mAChR, as they competed with binding of specific radioligand to mAChR and interacted with the second extracellular loop of human M₂ mAChR. Moreover, affinity purified anti-M₂ peptide IgG from group I, in common with monoclonal antihuman M₂ mAChR, recognised bands with a molecular weight corresponding to colon mAChR. This antibody also displayed an agonist-like activity, increasing basal tone and decreasing cAMP accumulation. Both effects were blunted by AF-DX 116 and neutralised by the synthetic peptide.

CONCLUSIONS In chagasic patients with megacolon there are antibodies that can recognise and activate M₂ mAChR. The implications of these autoantibodies in the pathogenesis of chagasic megacolon is discussed.