Increased levels of inhibitory G protein in myocardium with heart failure.
To identify any differences in inhibitory G protein (Gi) attributable to species or the cause of heart failure, we studied the changes in this protein in different animal models of heart failure: 1) different species; rats vs. hamsters (F1B) with cardiomyopathy induced by adriamycin (ADR) and 2) different etiologies; rats with ischemic heart failure (IHD) due to coronary artery ligation vs. rats with cardiomyopathy induced by ADR and F1B (20-week-old) hamsters with cardiomyopathy induced by ADR vs Syrian hamsters BIO 14.6 (40-week-old) with genetic cardiomyopathy, using Western blotting methods and ADP-ribosylation. We also sought to determine whether changes in the amount of Gi protein reflected the regulation of adenylate cyclase. The amount of immunodetectable Gi rose by 35% (p < 0.05) in ADR rats, 25% (p < 0.05) in ADR hamsters, 15% (p < 0.05) in IHD rats, and 28% (p < 0.05) in BIO 14.6 hamsters, as compared with control rats, F1B (20-week-old) hamsters, sham-operated control rats, and F1B (40-week-old) hamsters, respectively. Assessment of Gi by pertussis toxin-catalyzed ADP-ribosylation revealed increases in Gi of 24% (p < 0.05) in ADR rats and of 44% (p < 0.05) in BIO 14.6 hamsters, as compared with their respective controls. Gi function, as assayed by the acetylcholine-induced inhibition of adenylate cyclase, also increased. Thus, Gi protein appears to contribute to the changes in signal transduction in myocardium with heart failure.
Kawamoto
H
H
First Department of Internal Medicine, Hyogo College of Medicine, Japan.
Ohyanagi
M
M
Nakamura
K
K
Yamamoto
J
J
Iwasaki
T
T
D000262:Adenylyl Cyclases / Q000032:analysis; D000818:Animals; D015153:Blotting, Western; D009202:Cardiomyopathies / Q000150:complications; D006224:Cricetinae; D019204:GTP-Binding Proteins / Q000032:analysis* / Q000502:physiology; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008647:Mesocricetus; D017202:Myocardial Ischemia / Q000150:complications; D009206:Myocardium / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000032:analysis; D011976:Receptors, Muscarinic / Q000032:analysis; D015398:Signal Transduction; D013045:Species Specificity
D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases