Effects of gastrin on the histamine-secretory and proliferative activity of cultured carcinoid cells derived from the stomach of the rodent Mastomys natalensis.

The effects of gastrin on the synthesis and release of histamine and on cellular proliferation were investigated in a homotransplantable carcinoid tumor implanted in the rodent Mastomys natalensis and in cultured cells derived from the tumor. The homotransplanted tumor was immunopositive for histamine, synaptophysin and protein gene product 9.5, and its cells contained numerous secretory granules that were visualized by electron microscopy. When carcinoid cells were cultured in a medium with a high concentration of gastrin-I (10(4) pg/mL) for 7 days, large electron-dense secretory granules were characteristically observed in the cytoplasm. By contrast, only a few such granules and numerous secondary lysosomes were seen in cells that had been cultured in the same medium without gastrin-I. A high concentration of gastrin-I (10(4) pg/mL) significantly increased the release of histamine into the culture medium from the carcinoid cells compared with the control (P < 0.05). Cellular proliferation, as determined by monitoring the incorporation of [methyl-3H]-thymidine into the carcinoid cells increased significantly at lower concentrations of gastrin-I (10(2) and 10(3) pg/mL), (P < 0.05). At higher concentrations (10(4) pg/mL or more), gastrin-I had no effect on proliferation. These findings indicate that gastrin stimulates the synthesis and release of histamine by carcinoid cells, as well as their proliferation.