Beta-adrenergic agonists stimulate the synthesis of noncontractile but not contractile proteins in cultured myocytes isolated from adult rat heart.

Abstract

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.

Direct Binding of the β1 Adrenergic Receptor to the Cyclic AMP-Dependent Guanine Nucleotide Exchange Factor CNrasGEF Leads to Ras Activation

“…In these tumors, the activating mutations in both Gs␣ and the thyroid-stimulating hormone receptor (a GPCR) result in the constitutive activation of adenylyl cyclase (48). Furthermore, increases in cAMP levels, ␤1-AR function (17,42), and Ras activity (2,45) were independently reported in cardiac hypertrophy, but the underlying mechanisms are unknown. Thus, although speculative, it is possible that CNrasGEF is involved in pathological conditions where ␤1-AR, cAMP, or Gs␣ are implicated.…”

Comitogenic effect of catecholamines on rat cardiac fibroblasts in culture

“…through both a -and b-adrenoceptors, and that signalling Our results on the involvement of MAPK in the 1 pathways from the two receptors synergistically induced comitogenic response to NE are also in agreement with hypertrophy of neonatal rat cardiac myocytes. Furtherstudies describing the effect of MAPK in the induction of more, in isolated myocytes from the hearts of adult rats, proliferation after treatment of various cell types with b-adrenergic agonists stimulated protein synthesis [35]. different mitogens.…”

Electrical Stimulation of Neonatal Cardiac Myocytes Activates the NFAT3 and GATA4 Pathways and Up-regulates the Adenylosuccinate Synthetase 1 Gene

“…This valuable model system has allowed the biochemical and molecular characteristics of cardiac hypertrophy to be studied under experimentally controlled conditions (2, 4 -6). Neonatal cardiac myocytes display features of the hypertrophic response after stimulation with ␣-adrenergic agonists (7-9), endothelin-1 (10 -12), transforming growth factor-␤ (13), insulin-like growth factor (14), angiotensin II (3), and other hormonal stimuli (15,16). Stimulated cardiac myocytes undergo increases in cell size and in myofibrillar abundance with extensive parallel sarcomere alignment (4,8,17).…”