Abstract
The effect of verapamil treatment on the myocardial β-adrenergic adenylyl cyclase complex in acute canine Chagas' disease was investigated. Relative to uninfected animals, 30 days of infection with T. cruzi reduced myocardial adenylyl cyclase activity by over 75%. With continuous verapamil treatment, the infection-associated reduction in adenylyl cyclase activity was less than 50%. The individual components of the β-adrenergic receptor complex were characterized. Infection: (1) increased right ventricular (RV) β-adrenergic receptor (βAR) density five-fold; (2) decreased left ventricle βAR density by 20%; (3) reduced the proportion of high-affinity βAR receptors to the same extent in both left and right ventricles; (4) reduced α(s) by 50% as determined by Western blot analysis, increased α(il-3) but did not change a0; and (5) decreased the magnitude of pertussis-toxin-dependent [32P]ADP ribosylation by 60% as well as the proportion of [32P]ADP-ribose incorporated in a0. Verapamil treatment of infected animals restored RV βAR receptor density, α(s) and α(il-3) to control levels but had no influence on any aspect of pertussis-toxin-dependent [32P]ADP-ribosylation. Verapamil treatment of uninfected animals also: (1) increased β-adrenergic adenylyl cyclase activity; (2) increased βAR density in the RV but not the LV; (3) reduced high- to low-affinity β-adrenergic receptors; and (4) affected only α(i2) (50% decrease). The results indicate that the major actions of verapamil on the β-adrenergic adenylyl cyclase complex in acute canine Chagas' disease may help to account for its cardioprotective effects.
Original language | English (US) |
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Pages (from-to) | 931-941 |
Number of pages | 11 |
Journal | Journal of Molecular and Cellular Cardiology |
Volume | 28 |
Issue number | 5 |
DOIs | |
State | Published - May 1996 |
Externally published | Yes |
Keywords
- Chagas' cardiomyopathy
- Verapamil
- b-adrenergic receptor
ASJC Scopus subject areas
- Molecular Biology
- Cardiology and Cardiovascular Medicine