Alterations in acetylcholine receptors in experimental chagas' disease

Acetylcholine (ACH) receptors were studied to determine whether these receptors are affected during infections due to Trypanosoma cruzi in resistant and susceptible mice. Nicotinic ACH receptors were measured by the binding of [125I] alpha-bungarotoxin in skeletal muscle and brain tissues of two susceptible mouse strains (A/J and C3H) infected with the Brazil strain of T. cruzi. In skeletal muscle and brain tissues there were significant increases in alpha-bungarotoxin binding late but not early in infection. Infected resistant mice studied at 30 and 90 days after challenge showed no increase in alpha-bungarotoxin binding. Muscarinic ACH receptors were measured using [3H]quinuclidinyl benzilate. There were no significant changes in numbers of muscarinic ACH receptors in hearts and brains of infected mice. Pathologic studies revealed marked necrosis and many pseudocysts in skeletal muscle of C3H and A/J strain mice. Clinical denervation hypersensitivity occurs in Chagas' disease and is associated with an increase in ACH receptors. Our findings may provide a cellular basis for denervation hypersensitivity in Chagas' disease.