title: Altered liver α1-adrenoceptor density and phospholipase C activity in the human hepatocellular carcinoma.
abstract: The human hepatocellular carcinoma (HCC) is a common cancer with high mortality rate. We examined the density and coupling to phospholipase C (PLC) of the α(1)-adrenoceptors. In HCC liver, the α(1)-adrenoceptor density - as assessed by [³H]-Prazosin binding - was significantly reduced to about 75% when compared to non-adjacent non-tumorous liver (NA-NL) (P=0.0002). The decrease in maximal α(1)-adrenoceptor concentration (B(max)) was accompanied by a significant reduction in noradrenaline-stimulated PLC activity (P<0.032 versus NA-NL) (assessed by [³H]-PIP(2) hydrolysis). GTPγS-stimulated PLC activity in HCC livers did not statistically differ from NA-NL livers. NaF, which activates all G-proteins, stimulated PLC in both HCC and NA-NL livers to a similar extent. The altered noradrenaline-induced functional responsiveness of HCC livers was not reflected by changes in the binding affinity of [³H]-Prazosin for α(1)-adrenoceptors (NA-NL: 0.066 ± 0.010 pmol/l; tumour: 0.067 ± 0.020 pmol/l). These results demonstrate that human HCC causes profound alteration of the hepatic α(1)-adrenoceptor signal transduction pathway and may account for a negative cancer related metabolism of carbohydrates and wasting syndrome in tumour patients.
authors.affiliation: University of Leipzig, Department of Surgery II, Liebig Strasse 20a, Germany.
authors.forename: Woubet T
authors.initials: WT
authors.lastname: Kassahun
authors.forename: Bianca
authors.initials: B
authors.lastname: Günl
authors.forename: Sven
authors.initials: S
authors.lastname: Jonas
authors.forename: Fritz R
authors.initials: FR
authors.lastname: Ungemach
authors.forename: Getu
authors.initials: G
authors.lastname: Abraham
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000097:blood / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism*; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D018340:Receptors, Adrenergic, alpha-1; D000509:alpha-Fetoproteins; D010738:Type C Phospholipases