Norepinephrine modulates the growth‐inhibitory effect of transforming growth factor‐beta in primary rat hepatocyte cultures

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Abstract
TGF-beta is a potent inhibitor of EGF-induced DNA synthesis in primary rat hepatocyte cultures. Norepinephrine (NE) was shown to modulate this inhibition of DNA synthesis. It produced a five-fold increase, from 2.8 pM to 14.4 pM, in the ID50 for TGF beta. The effect was dose-dependent and was significant at concentrations of 10−6M NE and greater. The modulation by NE was mediated by the alpha1-adrenergic receptor as shown by the ability of the alpha1 antagonist prazosin to block the activity. This effect might be important during liver regeneration in allowing escape of hepatocytes from negative growth control exerted by TGF-beta.