Upregulation of alpha1A- and alpha1B-adrenergic receptor mRNAs in the heart of cardiomyopathic hamsters.
An increased density of alpha1-adrenergic receptors (AR) has been linked to the development of necrotic lesions in the heart of hamsters with hereditary cardiomyopathy. To determine whether this increase results from an upregulation of the receptor mRNA(s), Northern blot analyses were carried out in the heart of 60-day-old control and cardiomyopathic hamsters using selective DNA probes for the three subtypes of alpha1-ARs (alpha1A, alpha1B and alpha1D). Transcripts for the three alpha1-ARs were detected in both control and cardiomyopathic hamsters. A two-fold increase in the alpha1A- and alpha1B-AR mRNA levels was observed in the cardiomyopathic hearts when compared to controls. In contrast, no change in the alpha1D-AR mRNA level could be detected. The enhancement in alpha1A- and alpha1B-AR mRNA levels was paralleled by a 20% increase in the total number of alpha1-ARs, as assessed by [3H]prazosin radioligand binding assays. Competition binding assays using subtype selective ligands indicated that the increased density of both alpha1A and alpha1B receptors contributes to the total alpha1-AR upregulation. Taken together, these data suggest that the early development of hereditary cardiomyopathy in hamsters is accompanied by a specific overexpression of the alpha1A- and alpha1B-ARs. A discrete increase of the alpha1-AR density could contribute to eliciting coronary microspasms, therefore participating in the development of focal necrotic lesions that are characteristic of the hamster cardiomyopathic model.
Beaulieu
M
M
Département de Biochimie, Université de Montréal, Québec, Canada.
Brakier-Gingras
L
L
Bouvier
M
M
D000818:Animals; D001667:Binding, Competitive; D015152:Blotting, Northern; D009202:Cardiomyopathies / Q000378:metabolism*; D006224:Cricetinae; D005815:Genetic Code; D016015:Logistic Models; D008297:Male; D008647:Mesocricetus; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D011869:Radioligand Assay; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics*; D012016:Reference Values; D012044:Regression Analysis; D015854:Up-Regulation
D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1