Alterations of G protein function in cardiac tissues from streptozotocin-induced chronic diabetic rats

Abstract

1. 1. This study was performed to investigate G protein function in cardiac tissues from chronic diabetic rats by using pertussis toxin (PTX) and cholera toxin (CTX) as probes for G i and G s proteins, respectively. 2. 2. In the 10-week control group, i.v. injection of PTX significantly elevated the basal heart rate without having any effect on the chronotropic response of right atria to increasing concentrations of isoproterenol (ISO). In the 10-week diabetic rats, PTX treatment had no effect on the basal heart rate or on the response of right atria to ISO. In the 6-month groups, PTX did not exert any effects on basal or ISO-stimulated heart rate in either control or diabetic rat. 3. 3. The inhibitory effect of carbachol (CCH) on cardiac tension in ISO-stimulated left atria was completely abolished by i.v. injection of PTX in the 10-week groups (both control and diabetic rats). The same treatment, however, only slightly reduced the effect of CCH on left atria contraction in rats from 6-month groups. 4. 4. In both control and diabetic rats in the 10-week groups, incubation with CTX caused a significant increase in heart rate in right atria, and in developed cardiac tension in left atria preparations. The magnitude of the increase was the same in both control and diabetic rats. 5. 5. Studies carried out using ADP-ribosylation technique indicated that the amount of G i protein was not changed in the ventricular muscle of the 10-week diabetic rat. Labelling of G s protein could not be detected in either control or diabetic rat heart. 6. 6. These results suggest that the activity of G i proteins may be decreased in the right atria but not the left atria of the 10-week diabetic rats, although the amount of G i protein was not determined in the atria. The amount in the ventricular muscle did not change in the 10-week diabetic rats as indicated by ADP-ribosylation. G i proteins also seem to change with aging or development, but no difference in G i protein function was observed between the 6-month control and diabetic rats. G s protein appears to function normally in the diabetic rat heart. G protein alterations thus occur in diabetes, although the significance of G protein alterations in the development of cardiac disorders remains to be determined.