INVOLVEMENT OF NITRIC-OXIDE SYNTHASE AND PROTEIN-KINASE-C ACTIVATION ON CHAGASIC ANTIBODIES ACTION UPON CARDIAC CONTRACTILITY

We have already demonstrated the presence of antibodies in the sera of chagasic patients with the ability to interact with neurotransmitter receptors triggering several intracellular pathways of transduction si gnals. Here we show that, chagasic IgG induced protein kinase C (PKC) translocation to rat cardiac membranes and this effect was inhibited b y muscarinic cholinergic blockers atropine and AF-DX 116 pointing to t he participation of M(2) receptors in this effect. It was also able to stimulate nitric oxide synthase (NOS) activity and this action was bl unted by phospholipase C (PLC) and PKC inhibitors indicating that the production of nitric oxide (NO) would be the consequence of the cascad e of enzymatic pathways triggered by mAChR activation. PKC and NOS act ivities were involved in chagasic IgG negative inotropic actions on ra t isolated myocardium as its effects were blunted by staurosporine and L-N-monomethyl arginine. Furthermore, low concentrations of chagasic IgG inhibited the cardiac mechanical action of carbachol in a non-comp etitive manner. These data suggested that PKC activation in myocardium by chagasic IgG would be involved in its physiological actions by mod ulating NOS activity. The participation of PKC-mediated phosphorylatio n of mAChR leading to receptor desensitization as one of the causes of dysautonomia is also discussed.