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.