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 hista-mine and on cellular prollferatlon were Investigated in a homotransplantable carcinold 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 vlsualized by electron microscopy. When carcinold cells were cultured in a medlum with a high concentration of gastrin-1 (10⁴ 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 seaondary lysosomes were seen in cells that had been cultured in the same medium without gastrin-1. A high concentration of gastrin-1 (10⁴ pg/mL) slgniflcantly Increased the release of histamine Into the culture medium from the carcinoid cells compared wlth the control (P<0.05). Cellular proIiferation, as determlned by monitoring the incorporatlon of methyl-³H]-thymidine into the carcinold cells Increased sig nfficantly at lower concentrations of gastrin-1 (10² and 10³ pg/ mL), (P<0.05). At higher concentratlons (10⁴ pg/mL or more), gastrin-1 had no effect on proliferatlon. These findings Indicate that gastrin stimulates the synthesis and release of histamlne by carclnoid cells, as well as their proliferation.