Antibodies from Trypanosoma cruzi infected mice recognize the second extracellular loop of the beta 1-adrenergic and M2-muscarinic receptors and regulate calcium channels in isolated cardiomyocytes

Sera from T. cruzi infected mice were tested in an enzyme immunoassay on peptides corresponding to the second extracellular loops of the beta 1-, the beta 2-adrenergic receptor and the M2 muscarinic receptor. All sera of mice (4/4) in the acute phase recognized the beta 1-adrenergic receptor and the...

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Bibliographic Details
Published in:Molecular and cellular biochemistry 1996-10, Vol.163-164, p.107-112
Main Authors: Mijares, A, Verdot, L, Peineau, N, Vray, B, Hoebeke, J, Argibay, J
Format: Article
Language:English
Subjects:
Animals
Antibodies, Protozoan - metabolism
Autoantibodies - analysis
Calcium Channels - metabolism
Chagas Disease - immunology
Cyclic AMP - metabolism
Electrophysiology
Epitopes - analysis
Guinea Pigs
Heart - parasitology
Immunoenzyme Techniques
Male
Mice
Mice, Inbred BALB C
Myocardium - metabolism
Patch-Clamp Techniques
Propranolol - pharmacology
Protein Conformation
Receptor, Muscarinic M2
Receptors, Adrenergic, beta-1 - metabolism
Receptors, Muscarinic - metabolism
Structure-Activity Relationship
Trypanosoma cruzi - immunology
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Summary:Sera from T. cruzi infected mice were tested in an enzyme immunoassay on peptides corresponding to the second extracellular loops of the beta 1-, the beta 2-adrenergic receptor and the M2 muscarinic receptor. All sera of mice (4/4) in the acute phase recognized the beta 1-adrenergic receptor and the M2 muscarinic receptor peptides but not the beta 2-adrenergic receptor peptide. The same peptides were recognized during the chronic phase in half of the mice (6/12). The immunoglobulin fractions of the mice were tested for their activity on L-type Ca++ channels of isolated guinea-pig cardiomyocytes using the whole-cell patch clamp technique. The immunoglobulin fractions of acute phase mice were able to activate the Ca++ channels by stimulation of the beta-adrenergic receptors, as assessed by inhibition with propranolol. Those of the chronic phase mice reduced the Ca++ current by stimulation of the muscarinic receptors, as assessed by inhibition with atropine. These results confirm the existence of functional epitopes on the second extracellular loops of both receptors. They suggest that, as in humans, the parasite is able to elicit functional autoantibodies against these epitopes. They give evidence that these autoantibodies mediate their physiological effects by modulating the cAMP activated Ca++ channels.
ISSN:0300-8177
1573-4919
DOI:10.1007/BF00408646