Changes in myocardial beta1-adrenergic receptor and stimulatory G-protein gene expression after chronic treatment with doxorubicin in rat.
The gene expression of beta(1)-adrenergic receptor (beta(1)AR) and stimulatory G-protein Gsalpha in ventricle after chronic treatment with doxorubicin (DOX) in rat was investigated. The rats were treated with DOX in a dose of 2.5 mg/kg once a week for 5 weeks, the cumulative dose being 12.5 mg/kg. Two weeks after the last injection, the positive inotropic effect of isoproterenol was noticeably decreased in left atrial muscle preparations isolated from DOX-treated rats. Northern blot hybridization showed that the mRNA transcripts of beta(1)AR and Gsalpha, important signal transduction elements for regulating heart rate and contractility, were significantly decreased in the ventricle of DOX-treated rats. Thus, chronic treatment with DOX decreases the gene expression levels of myocardial beta(1)AR and Gsalpha.
Kizaki
Keiichiro
K
Department of Veterinary Pharmacology, School of Veterinary Medicine and Animal Sciences, Kitasato University, Aomori, Japan.
Akatsuka
Keiko
K
Momozaki
Masami
M
Fujimori
Yuuki
Y
Uchide
Tsuyoshi
T
Temma
Kyosuke
K
Hara
Yukio
Y
D000818:Animals; D015152:Blotting, Northern; D001835:Body Weight; D002316:Cardiotonic Agents / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006352:Heart Ventricles / Q000033:anatomy & histology / Q000378:metabolism*; D007545:Isoproterenol / Q000378:metabolism; D023421:Models, Animal; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics / Q000378:metabolism*
D002316:Cardiotonic Agents; D012333:RNA, Messenger; D018342:Receptors, Adrenergic, beta-1; D004317:Doxorubicin; D019205:GTP-Binding Protein alpha Subunits, Gs; D007545:Isoproterenol