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Noradrenergic modulation of albumin expression in growth-stimulated adult rat hepatocytes in primary culture

✍ Scribed by Isabel Fabregat; Carmen De Juan; CÉSar Roncero; Manuel Benito

Publisher
John Wiley and Sons
Year
1994
Tongue
English
Weight
603 KB
Volume
158
Category
Article
ISSN
0021-9541

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✦ Synopsis

Serum albumin is the most abundant protein synthesized by liver cells, and its production is a reliable indicator of the differentiated state of hepatocytes. We have recently shown that fetal rat hepatocytes cultured under proliferative conditions, i.e., in the presence of EGF, responded to glucagon and noradrenaline increasing albumin protein and mRNA levels (de Juan et al., 1992,. J. Cell. Physiol., 152.95-101). This effect was mimicked by agents that increase cyclic AMP levels. In this report, we show that in regenerating liver, noradrenaline modulation of albumin expression seems to be different. Hepatocytes from hepatectomized rats were cultured at low cell density and in the presence of EGF. Under these conditions, noradrenaline, which acted synergistically with EGF increasing DNA synthesis (de Juan et al., 199%. Exp. Cell. Res., 202:495-500), produced a decrease in albumin mRNA levels. This effect was dose-dependent, being maximum at 1 pM noradrenaline. Noradrenergic effect seemed to be mediated by a,-receptors, because it was blocked by prazosin, but not by propranolol.

Other Ca2+-increasing agents, as vasopressin, angiotensin II, or ATP, did not produce any effect. However, albumin mRNA levels decreased when the cells were incubated in the presence of tetradecanoyl phorbol-13-acetate (TPA), In addition, noradrenergic modulation of albumin expression was blocked by staurosporine, a protein kinase inhibitor with relative specificity for protein kinase C.

Thus we can conclude that the role of noradrenaline on the regulation of liver growth and differentiation changes from fetal to adult life. This change is probably due to its action on different receptors: @-receptors in fetal hepatocytes and a,-receptors in the adult liver. o 1994 Wiley-Liss, Inc.

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