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 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.