EFFECTS OF GASTRIN ON THE HISTAMINE-SECRETORY AND PROLIFERATIVE ACTIVITY OF CULTURED CARCINOID CELLS DERIVED FROM THE STOMACH OF THE RODENTMASTOMYS-NATALENSIS

The effects of gastrin on the synthesis and release of histamine and o n cellular proliferation were investigated in a homotransplantable car cinoid tumor implanted in the rodent Mastomys natalensis and in cultur ed cells derived from the tumor. The homotransplanted tumor was immuno positive for histamine, synaptophysin and protein gene product 9.5, an d its cells contained numerous secretory granules that were visualized by electron microscopy. When carcinoid cells were cultured in a mediu m with a high concentration of gastrin-l (10(4) pg/mL) for 7 days, lar ge electron-dense secretory granules were characteristically observed in the cytoplasm. By contrast, only a few such granules and numerous s econdary lysosomes were seen in cells that had been cultured in the sa me medium without gastrin-l. A high concentration of gastrin-l (10(4) pg/mL) significantly increased the release of histamine into the cultu re medium from the carcinoid cells compared with the control (P<0.05). Cellular proliferation, as determined by monitoring the incorporation of [methyl-H-3]-thymidine into the carcinoid cells increased signific antly at lower concentrations of gastrin-l (10(2) and 10(3) pg/mL), (P <0.05). At higher concentrations (10(4) pg/mL or more), gastrin-l had no effect on proliferation. These findings indicate that gastrin stimu lates the synthesis and release of histamine by carcinoid cells, as we ll as their proliferation.