Participation of nitric oxide signalling system in the cardiac muscarinic cholinergic effect of human chagasic IgG

STERIN-BORDA, L.; VILA ECHAGÜE, A.; GOIN, J.C.; PÉREZ LEIRÓS, C.; GENARO, A.; CREMASCHI, G.; BORDA, E.

Eilat, Israel

Congreso; 1st Congress of the Federation of the Israeli Societies of Experimental Biology (FISEB); 1995

Federation of the Israeli Societies of Experimental Biology (FISEB)

The possible role of altered humoral immune response in the chronic chagasic cardioneuromyopathy was examined by analyzing the interaction of IgG from T. cruzi infected patients with cardiac muscarinic cholinergic receptors (mAchR). Human chagasic IgG activating M2 mAChR simulated the agonist actions, exerting negative inotropic effect, activation of phosphoinositide turnover, stimulation of nitric oxide synthase (NOS) and increased production of cGMP. Inhibitors of phospholipase C, protein kinase C, calcium-calmodulin, NOS and guanilate cyclase activities prevented the chagasic IgG modification of intracellular events associated with specific receptor activation. In addition, sodium nitroprusside, isosorbide and 8-bromo cyclic GMP mimicked the chagasic IgG effect associated with cholinergic-mediated cellular transmembrane signals. In SDS-PAGE and immunoblotting analysis, chagasic sera recognized a band of 70-75 kDa. The major protein recognized by chagasic IgG had an Rf coincident with an apparent molecular weight similar to that of the mAChRs, disappearing with atropine. It is possible that chronic interaction of chagasic IgG with myocardial mAChR, behaving as a muscarinic agonist and inducing release of nitric oxide, leads to the cell dysfunction or tissue damage.