Alterations of G protein function in cardiac tissues from streptozotocin-induced chronic diabetic rats.
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 Gs proteins, respectively. 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. 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. 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. 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 Gs protein could not be detected in either control or diabetic rat heart.(ABSTRACT TRUNCATED AT 250 WORDS)
Hei
Y J
YJ
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Diamond
J
J
McNeill
J H
JH
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D019204:GTP-Binding Proteins / Q000502:physiology*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D037342:Pertussis Toxin; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D013311:Streptozocin; D002772:Cholera Toxin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins