Norepinephrine modulates the growth-inhibitory effect of transforming growth factor-beta in primary rat hepatocyte cultures.
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(-6)M NE and greater. The modulation by NE was mediated by the alpha 1-adrenergic receptor as shown by the ability of the alpha 1 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.
Houck
K A
KA
Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710.
Cruise
J L
JL
Michalopoulos
G
G
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D015291:Transforming Growth Factors
D010455:Peptides; D015291:Transforming Growth Factors; D009638:Norepinephrine