Autoregulation of McA-RH7777 Hepatoma Cell Proliferation by Histamine

Previous studies have suggested that histamine (HA) acts as an autocrine growth factor. We have explored the modulation of cell proliferation by HA using McA-RH7777 hepatoma cells. High L-histidine decarboxylase (HDC) expression and HA syn-thesis were found in McA-RH7777 cells. Whereas extracellular HA reached submicromolar concentrations, intracellular levels were very low, indicating that HA was secreted by the cells. McA-RH7777 cells also express H3-receptor (H3R) transcripts and proteins. Reverse transcriptase-polymerase chain reaction analysis detected only transcripts for the long isoform. Immu-nocytochemistry performed with a selective H3R antibody showed that most cells were immunoreactive. H3R binding sites (Bmax 30 fmol/mg protein) were identified when [ 125I