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Biomedical subjects

E Borda

Publications and source records attributed to E Borda.

116 records · Page 7Linked to original sources
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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 signals. Here we show that, chagasic IgG induced protein kinase C (PKC) translocation to rat cardiac membranes and this effect was inhibited by muscarinic cholinergic blockers atropine and AF-DX 116 pointing to the participation of M2 receptors in this effect. It was also able to stimulate nitric oxide synthase (NOS) activity and this action was blunted by phospholipase C (PLC) and PKC inhibitors indicating that the production of nitric oxide (NO) would be the consequence of the cascade of enzymatic pathways triggered by mAChR activation. PKC and NOS activities were involved in chagasic IgG negative inotropic actions on rat 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-competitive manner. These data suggested that PKC activation in myocardium by chagasic IgG would be involved in its physiological actions by modulating NOS activity. The participation of PKC-mediated phosphorylation of mAChR leading to receptor desensitization as one of the causes of dysautonomia is also discussed.

Animals↗
PubMedDate not supplied

Circulating antibodies against neonatal cardiac muscarinic acetylcholine receptor in patients with Sjögren's syndrome.

Isolated congenital heart block may be associated with Primary Sjögren's Syndrome. In this work we demonstrated that IgG present in the sera of patients with Primary Sjögren's Syndrome (PSS) could bind and activate muscarinic acetylcholine receptors of rat neonatal atria. These antibodies were able to inhibit in a irreversible manner the binding of 3H-QNB to muscarinic cholinergic receptors of purified rat atria membranes. Moreover, IgG from PSS individuals could modify biological effects mediated by muscarinic cholinoceptors activation, i.e. decrease contractility and cAMP and increase phosphoinositide turnover and cGMP. Atropine blocked all of these effects and carbachol mimicked them; confirming muscarinic cholinergic receptors-mediated PSS IgG action. Neither binding nor biological effect were obtained using adult instead of neonatal rat atria. IgG from sera of normal women were not effective in the studied system. The prevalence of cholinergic antibody was 100% in PSS and was independent of Ro/SS-A and La/SS-B antibodies. It could be concluded that antibody against muscarinic cholinergic receptors may be another serum factor to be considered in the pathophysiology of the development of congenital heart block.

Adult↗
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Alloimmunization-induced changes in beta-adrenoceptor expression and cAMP on B lymphocytes.

In this report we have examined the effect of alloimmunization on beta-adrenergic expression in lymphocytes. We have observed a variation in the number of beta-adrenoceptors (Bmax) according to the degree of immunization without modifications in their affinity (Kd). This phenomenon was accompanied with parallel variations of intracellular cAMP levels. A decrease in Bmax values was observed during the first and second immunizations. Then the Bmax began to increase, exceeding control values up to the fourth and fifth immunizations, and remaining constant at the sixth immunizations. Only B cell-enriched populations showed variation in Bmax values of beta-adrenoceptors with alloimmunization. In contrast, the Bmax values of T cell-enriched populations did not change. Kd values were similar in all cell types tested. The number of binding sites was not dependent on the animal's age. Modifications in cAMP levels of B cell-enriched populations were correlated with changes in beta-adrenoceptor expression. These results suggest that beta-adrenoceptor expression and cAMP intracellular levels in B cell-enriched populations vary with the number of alloimmunizations. In addition, the antibody synthesis induced by allogenic stimulus was inversely proportional to the number of beta-adrenoceptors expressed on B cells. Perhaps these findings are evidence of a control mechanism that regulates antibody synthesis during the immune response.

Animals↗
PubMedDate not supplied

Detection of mRNA encoding H(1) receptor and iNOS by RT-PCR in autoimmune myocarditis with special reference to changes in heart contractility.

Cardiac tissue from autoimmune myocarditis mice was studied to evaluate the expression and biological activity of mRNA encoding H(1) receptor and iNOS. BALB/c inbred mice were immunized with heart protein and sacrificed at 20, 45 and 50 days post immunization. Heart contractility studies and RT-PCR assays were performed. Heart from autoimmune myocarditis mice show mRNA iNOS-related dysfunction with a decrease in heart contractility. This effect was accompanied with an increase production of cyclic GMP and was improved by treating autoimmune mice with an inhibitor of iNOS activity. In addition, autoimmune myocardium expressed an active histamine H(1) receptor mRNA coupled to phospholipase C. The activation of H(1) receptor by ThEA stimulated both phosphoinositide hydrolysis and heart contractility. Normal myocardium did not expressed neither iNOS mRNA nor H(1) receptor mRNA. In conclusions: the development of autoimmune cardiac dysfunction was associated with the expression of iNOS mRNA, cyclic GMP accumulation and the expression of an active histamine H(1) receptor mRNA with increase production of inositol phosphates. These protein emergence during the course of autoimmune myocarditis may be involved a distinct compensatory mechanism operating in this disease.

Animals↗
PubMedDate not supplied

Modification of cholinergic-mediated cellular transmembrane signals by the interaction of human chagasic IgG with cardiac muscarinic receptors.

The possible role of altered humoral immunity in cardiac Chagas' disease was examined by analyzing the interaction of IgG and the corresponding F(ab')2 from Trypanosoma cruzi-infected patients with cardiac muscarinic cholinergic receptors (mAchR). Human chagasic IgG and its F(ab')2 simulated the agonist actions triggering the biological effects associated with cholinergic-mediated cellular transmembrane signals, i.e. stimulation of cGMP, inhibition of cAMP and a decrease in atrial contractility. Atropine blunted all of these effects while pertussis toxin prevented the inhibition of cAMP and contractility confirming the G-regulatory-protein-mediated response in the interaction of chagasic antibodies with cardiac mAchR. In addition, chagasic IgG and its F(ab')2 behaved as partial agonists activating the specific receptor and inhibiting in a noncompetitive manner the activity of an exogenous agonist (pilocarpine). Moreover, chagasic IgG immunoprecipitated the mAchR solubilized from cardiac membrane in a concentration-dependent fashion. By means of SDS-PAGE and immunoblotting analysis, chagasic serum was shown to recognize a band of approximately 75 kD. The electrophoretic studies of prelabeled immunoprecipitated proteins revealed a peak of [3H] propylbenzilylcholine mustard with an apparent molecular weight similar to that of mAchR, which disappeared in the presence of atropine. The presence of these antibodies in the serum of chagasic patients could explain the progressive receptor blockade in the parasympathetic branch of the cardiac autonomic nervous system associated with the cardioneuromyopathy described in the course of Chagas' disease.

Antibodies↗