Altered liver α1-adrenoceptor density and phospholipase C activity in the human hepatocellular carcinoma

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 alpha(1)-adrenoceptors. In HCC liver, the alpha(1)-adrenoceptor density - as assessed by [H-3]-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 alpha(1)-adrenoceptor concentration (B-max) was accompanied by a significant reduction in noradrenaline-stimulated PLC activity (P<0.032 versus NA-NL) (assessed by [H-3]-PIP2 hydrolysis). GTP gamma S-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 [H-3]-Prazosin for alpha(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 alpha(1)-adrenoceptor signal transduction pathway and may account for a negative cancer related metabolism of carbohydrates and wasting syndrome in tumour patients. (C) 2011 Elsevier B.V. All rights reserved.