Chagasic sera alter the effects of ouabain on isolated rat atria. Participation of adrenergic mechanisms

Sterin‐Borda, Leonor; Canga, Liliana; Borda, Enri; Cossio, Patricio M.; Diez, C.; Arana, Roberto M.; Gimeno, A.L.

doi:10.1016/0014-2999(81)90596-3

Cited by 13 publications

(3 citation statements)

References 13 publications

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“…To evaluate the effect of chagasic antipeptide IgG on cardiac intracellular signals coupled to mAChRs, cGMP and cAMP production was measured. As shown in Table 2, there was a significant increase in cGMP and a decrease in cAMP production by atria exposed to antipeptide cha- (10,13,14,27,28). Some of these antibodies react against cardiac 3-adrenergic receptors (29,30) and others react with mAChRs (10-13) of the heart.…”

Section: Action On Intracellular Camp and Cgmp Productionmentioning

confidence: 86%

Interaction of human chagasic IgG with the second extracellular loop of the human heart muscarinic acetylcholine receptor: functional and pathological implications

et al. 1997

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Circulating antibodies from human and murine chagasic sera are able to interact with myocardium-activating neurotransmitter receptors. Here we reported the presence of autoantibodies against the second extracellular loop of the human heart muscarinic acetylcholine receptors (mAChR) in patients with Chagas' disease by using a synthetic 24-mer peptide in immunoblotting and enzyme immunoassay. Affinity-purified antipeptide IgG from chagasic patients, similar to monoclonal antihuman M2 mAChR, recognized bands with a molecular weight corresponding to the cardiac mAChR. The binding was inhibited by the peptide, assessing the specificity of the interaction. The antipeptide autoantibody also displayed an "agonist-like" activity modifying the intracellular events associated with mAChR activation, i.e., decreased contractility, increased cGMP, and decreased cAMP production. All of these effects on rat atria by chagasic antipeptide autoantibodies resemble the effects of the authentic agonist and those of the total polyclonal chagasic IgG, being selectively blunted by atropine and neutralized by the synthetic peptide corresponding in aminoacid sequence to the second extracellular loop of the human M2 mAChR. A clinical relevance of these findings is demonstrated by a strong association between the existence of circulating antipeptide autoantibodies in chagasic patients and the presence of dysautonomic symptoms, making these autoantibodies a proper early marker of heart autonomic dysfunction.

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Section: Action On Intracellular Camp and Cgmp Productionmentioning

confidence: 86%

Interaction of human chagasic IgG with the second extracellular loop of the human heart muscarinic acetylcholine receptor: functional and pathological implications

et al. 1997

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“…Adequate proof has been presented supporting the existence of autoantibodies against β 1 18‐22 and muscarinic cholinergic 23‐27 receptors in the sera of chagasic patients, which are able to activate the signal transduction system coupled to these receptors and reflect the biological effect of the antibodies.…”

Section: Distribution Of Antibodies From Chagasic Sera Directed Againmentioning

confidence: 95%

Role of Neurotransmitter Autoantibodies in the Pathogenesis of Chagasic Peripheral Dysautonomia

Sterin‐Borda

Borda

2000

Annals of the New York Academy of Sciences

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A BSTRACT : Chagas' disease is caused by a parasite, Trypanosoma cruzi , which is widely distributed in South and Central America. Dysautonomias, derangements of sympathetic and parasympathetic nervous system function, are seen fairly often during the chronic course of Chagas' disease. Many infected subjects developed, in the course of the disease, neurogenic cardiomyopathy or digestive damage. Our investigations show the existence of circulating antibodies in Chagas' disease that bind to ␤ -adrenergic and muscarinic cholinergic receptor (mAChR). The neurotransmitter receptor-autoantibody interaction triggers in the cells intracellular signal transductions that alter the physiological behavior of the target organs, leading to tissue damage. Moreover, the deposit of autoantibodies behaving as agonists induces desensitization and/or down regulation of the receptors. This in turn can lead to a progressive blockade of them with sympathetic and parasympathetic denervation. Using synthetic peptides for immunoblotting and enzyme immunoassay, we demonstrated that these autoantibodies reacted against the second extracellular loop of the human heart ␤ 1 adrenoceptor and M 2 cholinoceptor. Also, the corresponding affinity-purified antipeptide antibodies displayed an agonist-like activity associated with specific receptor activation. A strong association between circulating antipeptide M 2 mAChR autoantibodies and the presence of patients' low heart rate variablity index, bradycardia and cardiac or esophageal autonomic dysfunction in chronic chagasic patients was verified. This fact make these antipeptide antibodies a proper marker of cardiac neuromyopathy and achalasia.

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“…As previously reported [29], concentrations of ouabain which produce only positive inotropic effects without changes in the resting tension (contracture) were con sidered as non-toxic. An increase in resting tension (contracture) was assumed to be the toxic influence of ouabain [21,22].…”

Section: Atrial Contractilitymentioning

confidence: 99%

Erythropoietin Modified the Cardiac Action of Ouabain in Chronically Anaemic-Uraemic Rats

Wald

Gutnisky²,

Borda³

et al. 1995

Nephron

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The results of the studies reported here demonstrate the cardiac non-haematopoietic effect of erythropoietin, providing a new physiological function of the hormone. We demonstrate that myocardium from rat with chronic renal failure (CRF) showed an abnormal reponse to ouabain associated with an inhibition of cardiac Na⁺/K⁺/ATPase activity and with a decrease in the high affinity ³H-ouabain binding sites. The extent to which both actions were improved with the recombinant human erythropoietin (rHuEpo) treatment suggests that the lack of the hormone is responsible for this phenomenon. The fact is that neither contractile nor enzymatic action of rHuEpo was accompanied with the improvement of the functional renal and haematologic parameters, indicating a primary effect on myocardial contractile function of rHuEpo, independent of the anaemic and uraemic state of the animal. The reason why erythropoietin is able to modulate directly the cardiac Na⁺/K⁺ pump makes it possible to conclude that the lack of erythropoietin in CRF may be at least in part responsible for the inhibition of cardiac enzymes, altering the contractile behaviour of the heart.

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Chagasic sera alter the effects of ouabain on isolated rat atria. Participation of adrenergic mechanisms

Cited by 13 publications

References 13 publications

Interaction of human chagasic IgG with the second extracellular loop of the human heart muscarinic acetylcholine receptor: functional and pathological implications

Interaction of human chagasic IgG with the second extracellular loop of the human heart muscarinic acetylcholine receptor: functional and pathological implications

Role of Neurotransmitter Autoantibodies in the Pathogenesis of Chagasic Peripheral Dysautonomia

Erythropoietin Modified the Cardiac Action of Ouabain in Chronically Anaemic-Uraemic Rats

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