Beta-adrenergic agonists stimulate the synthesis of noncontractile but not contractile proteins in cultured myocytes isolated from adult rat heart.
The effect of catecholamines on adult myocardial protein synthetic activity was studied by use of an experimental model of isolated adult rat cardiac myocytes maintained in culture for 1-6 days. During this period, the majority of myocytes retained their rod-shaped morphology, but the cell number decreased progressively (50% of the initial density after 2 days in culture). Between day 1 and day 3 in culture, the specific synthetic activities of total proteins and of electrophoretically purified myosin heavy chain and actin ([14C] phenylalanine incorporation into protein, in disintegrations per minute per microgram protein) decreased (-19%,-32%, and -73%, respectively). Addition of isoproterenol or norepinephrine (10 nM) from the onset of the culture for 3 days increased the specific activity of both total and noncontractile proteins (greater than 20%) but had no effect on the specific activity of myosin heavy chain and actin when compared with 3-day cultured control cells. beta-Adrenergic receptors are specifically required to mediate this increase in total protein synthesis. This finding was demonstrated by the inhibitory effects of propranolol; neither prazosin nor yohimbine showed any effect. The pattern of synthesized protein during adrenergic stimulation was qualitatively evaluated by use of [35S]methionine incorporation and gel electrophoresis. The general pattern of labeled proteins did not differ significantly from that of control cells; this occurrence suggests that isoproterenol harmoniously stimulates the synthesis of noncontractile proteins. These findings demonstrate that low doses of beta-adrenergic agonists have an anabolic effect on adult cardiac quiescent myocytes that do not affect the major contractile proteins. Regulation of myofibrillar protein synthesis may be more dependent on myocyte contractile activity.
Dubus
I
I
INSERM U127, Hôpital Lariboisière, Paris, France.
Samuel
J L
JL
Marotte
F
F
Delcayre
C
C
Rappaport
L
L
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D003285:Contractile Proteins / Q000096:biosynthesis*; D007545:Isoproterenol / Q000494:pharmacology; D009124:Muscle Proteins / Q000096:biosynthesis*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats
D000318:Adrenergic beta-Agonists; D003285:Contractile Proteins; D009124:Muscle Proteins; D007545:Isoproterenol; D009638:Norepinephrine