Chagasic IgG binding with cardiac muscarinic cholinergic receptors modifies cholinergic-mediated cellular transmembrane signals.
The interaction of the IgG from Trypanosoma cruzi-infected mice (chagasic IgG) with cardiac cholinergic receptors by means of specific radioligand binding and by production of cholinergic-mediated cellular transmembrane signals was characterized. Chagasic IgG inhibited, in a noncompetitive manner, the binding of [3H]quinuclidinyl benzilate to the cardiac membrane. Moreover, chagasic IgG could modify all of the muscarinic cholinergic effects mediated by a G regulatory protein, i.e., decrement of atria contractility, inhibition of cAMP, or activation of the turnover of phosphoinositides via phospholipase C. The cGMP production was also increased by the antibody. The data demonstrated that chagasic IgG interacting with cardiac muscarinic cholinergic receptor triggers the biological effects associated with cholinergic-mediated cellular transmembrane signals. The implications of the results in the pathogenesis of Chagas' myocarditis are discussed.
Sterin-Borda
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Centro de Estudios Farmacológicos y de Botánica (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina (CONICET), Buenos Aires.
Gorelik
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Borda
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D000818:Animals; D000906:Antibodies / Q000502:physiology; D001667:Binding, Competitive; D002598:Chagas Cardiomyopathy / Q000276:immunology*; D000242:Cyclic AMP / Q000032:analysis; D006152:Cyclic GMP / Q000032:analysis; D006325:Heart Atria / Q000276:immunology; D007140:Immunoglobulin Fab Fragments / Q000502:physiology; D007074:Immunoglobulin G / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000648:ultrastructure*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D010738:Type C Phospholipases / Q000494:pharmacology
D000906:Antibodies; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D011976:Receptors, Muscarinic; D000242:Cyclic AMP; D010738:Type C Phospholipases; D006152:Cyclic GMP