In an effort to correlate biochemical characteristics of the
beta-adrenergic receptor complex with myocardial function, mouse myocardial
GTP-binding proteins, specifically substrates for
pertussis toxin (PT), were analysed with regard to the influence of
infection with Trypanosoma cruzi, the causative agent of
Chagas' cardiomyopathy.
Infection was found to decrease in a non-uniform manner the magnitude of ADP-ribosylation in the PT substrates. High
detergent concentrations attenuated the
infection-associated decrease in PT-dependent ADP-ribosylation.
Infection also altered the kinetics of the PT-dependent ADP-ribosylation reaction from a time course wherein maximal PT-dependent ADP-ribosylation occurred after 12 h incubation in control animals to one in which maximal PT-dependent ADP-ribosylation occurred after 3 h incubation and thereafter declined. Immunochemical analysis of the PT-substrates revealed an
infection-associated decrease in alpha i1, alpha o, an increase in alpha i2 and no change in alpha i3.
Verapamil treatment, which prevents the clinical consequences of
infection, did not influence any of the
infection-associated changes in PT-dependent ADP-ribosylation of
GTP-binding protein substrates or their immunochemical properties. Complementary studies using isolated rat neonatal cardiocytes infected with the parasite further substantiated the finding that the
infection-associated decrease in PT-dependent ADP-ribosylation and the associated change in the kinetics of the reaction were properties uniquely associated with the presence of the parasite.