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 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.
Mijares
A
A
Laboratoire de Physiologie des Cellules Cardiaques et Vasculaires Faculté de Sciences Tours, France.
Verdot
L
L
Peineau
N
N
Vray
B
B
Hoebeke
J
J
Argibay
J
J
D000818:Animals; D000913:Antibodies, Protozoan / Q000378:metabolism*; D001323:Autoantibodies / Q000032:analysis; D015220:Calcium Channels / Q000378:metabolism*; D014355:Chagas Disease / Q000276:immunology*; D000242:Cyclic AMP / Q000378:metabolism; D004594:Electrophysiology; D000939:Epitopes / Q000032:analysis; D006168:Guinea Pigs; D006321:Heart / Q000469:parasitology*; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011433:Propranolol / Q000494:pharmacology; D011487:Protein Conformation; D043585:Receptor, Muscarinic M2; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014349:Trypanosoma cruzi / Q000276:immunology*
D000913:Antibodies, Protozoan; D001323:Autoantibodies; D015220:Calcium Channels; D000939:Epitopes; D043585:Receptor, Muscarinic M2; D018342:Receptors, Adrenergic, beta-1; D011976:Receptors, Muscarinic; D011433:Propranolol; D000242:Cyclic AMP