Patterns of alpha-1-adrenergic receptor expression in regenerating and neoplastic hepatic tissue.
As norepinephrine is a potent hepatocyte comitogen through binding to the alpha 1-adrenergic receptor, we have examined mRNA levels of the alpha 1a- and alpha 1b-adrenergic receptor subtypes in normal and regenerating rat hepatocytes as well as in several different rat hepatoma cell lines. All rat hepatomas examined lacked both alpha 1a- and alpha 1b-receptor message and receptor binding in radioligand binding experiments, suggesting that the growth of dedifferentiated neoplastic rat hepatocytes is not regulated by the alpha 1-adrenergic receptor. Interestingly, unlike the rat hepatomas analyzed, the human hepatocellular carcinoma cell line, HepG2, was positive for both alpha 1a and alpha 1b message at 4.5 kb, yet this cell line lacked receptor binding in radioligand binding assays. While normal and regenerating liver is negative for alpha 1a-receptor expression, it is positive for alpha 1b expression and is characterized by the presence of two bands at approximately 4.0 and 3.2 kb which peaked between 20 and 48 h after partial hepatectomy. A dramatic decrease in message level of the lower band and the continued presence of the upper band between 6 and 12 h after partial hepatectomy, and before the peak in DNA synthesis in regenerating rat liver, may correspond with observed differences in alpha 1-receptor function during liver regeneration.
Kost
D P
DP
Department of Pathology, Duke University Medical Center, Durham, N.C.
DeFrances
M C
MC
Lee
C R
CR
Michalopoulos
G K
GK
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D004247:DNA / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006498:Hepatectomy; D006801:Humans; D015151:Immunoblotting; D008099:Liver / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure; D008113:Liver Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011942:Receptors, Adrenergic, alpha / Q000032:analysis* / Q000235:genetics; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D012333:RNA, Messenger; D011942:Receptors, Adrenergic, alpha; D004247:DNA