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

1996 ◽  
Vol 163-164 (1) ◽  
pp. 107-112 ◽  
Author(s):  
Alfredo Mijares ◽  
Ludovic Verdot ◽  
Nicolas Peineau ◽  
Bernard Vray ◽  
Johan Hoebeke ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Calcium Channels ◽  
Muscarinic Receptors ◽  
Extracellular Loop ◽  
Isolated Cardiomyocytes ◽  
M2 Muscarinic Receptors

scholarly journals Immunocytochemical localization of M2 muscarinic receptors in rat ventricles with anti-peptide antibodies.

1994 ◽  
Vol 42 (3) ◽  
pp. 337-343 ◽  
Author(s):  
M Fu ◽  
W Schulze ◽  
W P Wolf ◽  
A Hjalmarson ◽  
J Hoebeke
Keyword(s):  
Muscarinic Receptor ◽  
Muscarinic Receptors ◽  
Receptor Protein ◽  
Extracellular Loop ◽  
Electron Microscopic ◽  
Major Band ◽  
Rat Cardiomyocytes ◽  
M2 Muscarinic Receptor ◽  
T Tubules ◽  
M2 Muscarinic Receptors

We produced antibodies against a synthetic peptide corresponding to amino acids 168-192 of the second extracellular loop of the M2 human muscarinic receptor in rabbits. In immunoblot, affinity-purified antibodies specifically recognized a major band of rat ventricular muscarinic receptor protein with a molecular weight of about 80 KD. This recognition could be blocked by pre-incubation with peptide. Moreover, with both light (LM) and electron microscopic (EM) immunocytochemistry techniques, muscarinic receptors were detected on sarcolemma and T-tubules of rat cardiomyocytes. In addition, immunoreactions were localized in membranes of capillaries. Likewise, these reactivities were abolished by pre-incubation with peptide. These results suggest that the antibodies against the second extracellular loop of human M2 muscarinic receptor could specifically recognize rat ventricular muscarinic receptor protein and could be a powerful tool to study the fate of this receptor under different pathological or physiological conditions.

scholarly journals Molecular mimicry between the immunodominant ribosomal protein P0 of Trypanosoma cruzi and a functional epitope on the human beta 1-adrenergic receptor.

1995 ◽  
Vol 182 (1) ◽  
pp. 59-65 ◽  
Author(s):  
I Ferrari ◽  
M J Levin ◽  
G Wallukat ◽  
R Elies ◽  
D Lebesgue ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Adrenergic Receptor ◽  
Molecular Mimicry ◽  
Autoimmune Response ◽  
Extracellular Loop ◽  
Western Blots ◽  
Carboxy Terminal ◽  
Ribosomal Protein P0 ◽  
Positive Chronotropic Effect

Sera from chagasic patients possess antibodies recognizing the carboxy-terminal part of the ribosomal P0 protein of Trypanosoma cruzi and the second extracellular loop of the human beta 1-adrenergic receptor. Comparison of both peptides showed that they contain a pentapeptide with very high homology (AESEE in P0 and AESDE in the human beta 1-adrenergic receptor). Using a competitive immunoenzyme assay, recognition of the peptide corresponding to the second extracellular loop (H26R) was inhibited by both P0-14i (AAAESEEEDDDDDF) and P0-beta (AESEE). Concomitantly, recognition of P0-beta was inhibited with the H26R peptide. Recognition of P0 in Western blots was inhibited by P0-14i, P0-beta, and H26R, but not by a peptide corresponding to the second extracellular loop of the human beta 2-adrenergic receptor or by an unrelated peptide. Autoantibodies affinity purified with the immobilized H26R peptide were shown to exert a positive chronotropic effect in vitro on cardiomyocytes from neonatal rats. This effect was blocked by both the specific beta 1 blocker bisoprolol and the peptide P0-beta. These results unambiguously prove that T. cruzi is able to induce a functional autoimmune response against the cardiovascular human beta 1-adrenergic receptor through a molecular mimicry mechanism.

Dysfunction of M2-muscarinic receptors in pulmonary parasympathetic nerves after antigen challenge

1991 ◽  
Vol 71 (6) ◽  
pp. 2255-2261 ◽  
Author(s):  
A. D. Fryer ◽  
M. Wills-Karp
Keyword(s):  
Muscarinic Receptors ◽  
Guinea Pigs ◽  
Antigen Challenge ◽  
Saline Control ◽  
Control Group ◽  
Vagus Nerves ◽  
Parasympathetic Nerves ◽  
Volume Blood ◽  
M2 Muscarinic Receptors ◽  
Stimulation Of

The effect of antigen challenge on the function of neuronal M2-muscarinic autoreceptors in the lungs was studied in anesthetized guinea pigs. Guinea pigs were injected intraperitoneally with saline (control group) or ovalbumin (10 mg/kg) on days 1, 3, and 5. One group of sensitized animals was challenged on days 20–25 with aerosolized ovalbumin for 5 min/day (challenged group), while another group of the sensitized animals was not challenged (sensitized group). On day 26 the animals were anesthetized, paralyzed, tracheostomized, and artificially ventilated. Pulmonary inflation pressure (Ppi), tidal volume, blood pressure, and heart rate were recorded. Both vagus nerves were cut, and electrical stimulation of the distal portions caused bronchoconstriction (measured as an increase in Ppi) and bradycardia. In the control group, pilocarpine (1–100 micrograms/kg iv) attenuated vagally induced bronchoconstriction by stimulating inhibitory M2-muscarinic receptors on parasympathetic nerves in the lungs. Conversely, blockade of these receptors with the antagonist gallamine (0.1–10 mg/kg iv) produced a marked potentiation of vagally induced bronchoconstriction. These results confirm previous findings. In the challenged guinea pigs, pilocarpine did not inhibit vagally induced bronchoconstriction. Furthermore, gallamine did not potentiate vagally induced bronchoconstriction to the same degree as in the controls. In the group of animals that was sensitized but not challenged, the potentiation of vagally induced bronchoconstriction by gallamine was identical to the controls. There was no increase in baseline Ppi in the sensitized or challenged animals compared with the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Involvement of M2 muscarinic receptors in relaxant response of circular muscle of mouse gastric antrum.

2006 ◽  
Vol 18 (3) ◽  
pp. 226-233 ◽  
Author(s):  
t. takeuchi ◽  
m. toyoshima ◽  
k. mukai ◽  
k. hagi ◽  
m. matsui ◽  
...  
Keyword(s):  
Muscarinic Receptors ◽  
Circular Muscle ◽  
Gastric Antrum ◽  
Relaxant Response ◽  
M2 Muscarinic Receptors
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