Prolonged treatment with isoproterenol causes a loss of myocardial Gsalpha mRNA expression.
We investigated the influence of chronic beta-adrenergic stimulation on Gsalpha protein gene expression and beta-adrenoceptor responsiveness in rat ventricular myocardium. The rats received twice-daily injections of 4 mg/kg isoproterenol (ISO) alone or with 8 mg/kg propranolol (PROP) for 4 days. In ventricular myocardium, Gsalpha mRNA expression decreased by 27% after ISO treatment. Dose-dependent (10 nM to 100 micro M) positive inotropic responses by ISO in the left papillary muscles were lower after ISO treatment than in saline-treated myocardium with decreases in ED50 values. PROP itself had no effect, although it antagonized both ISO-induced effects. These results suggest that impaired Galpha mRNA expression may explain the loss of cardiac Gsalpha subunit levels after chronic beta-adrenergic stimulation, and that these changes can provide one mechanism for the progress of long-term desensitization.
Miyamoto
A
A
Division of Clinical Pharmacy, University Hospital, Sapporo Medical University School of Medicine, Japan.
Ohshika
H
H
D000818:Animals; D004305:Dose-Response Relationship, Drug; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000096:biosynthesis* / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006321:Heart / Q000187:drug effects; D007545:Isoproterenol / Q000008:administration & dosage*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
D012333:RNA, Messenger; D019205:GTP-Binding Protein alpha Subunits, Gs; D007545:Isoproterenol