Bombesin has been reported to stimulate cholecystokinin (CCK) secretion from rat duodeno-jejunal I-cells. Bombesin was shown to activate mitogen-activated protein kinases (MAPKs) in cell types such as Swiss 3T3 fibroblasts and rat pancreatic acinar cells. No information is available on whether MAPK is activated in intestinal endocrine cells upon bombesin stimulation. This was studied by using the CCK-producing enteroendocrine cell line STC-1. Bombesin stimulated markedly and transiently both p42MAPK and p44MAPK, with a maximum at 2 min, and a decrease to basal levels within 10 min. As expected, bombesin stimulated MAPK kinase 1 (MEK-1) activity. Activation of protein kinase C (PKC) with PMA also stimulated p42MAPK, p44MAPK and MEK-1. Treatment of cells with PD 098059 (at 10 µM or 30 µM), which selectively inhibits MEK phosphorylation, blocked bombesin-induced p42MAPK and p44MAPK activation for at least 90 min. However, PD 098059 inhibited bombesin- and PMA-stimulated CCK secretion during the first 15 min, but failed to significantly reduce CCK release at later times. Inhibition of PKC with staurosporine, or PKC down-regulation by prolonged treatment with PMA, both drastically decreased MEK-1, p42MAPK and p44MAPK activation upon bombesin stimulation. Additionally, PKC activation appeared to be required for both MAPK-dependent (early) and -independent (late) CCK responses to bombesin. It is concluded that the early CCK secretory response of STC-1 cells to bombesin involves MAPK pathway activation through a PKC-dependent mechanism, whereas the late phase of bombesin-induced CCK secretion, that also requires PKC, appears to result from a MAPK-independent process.
Bombesin stimulates cholecystokinin secretion through mitogen-activated protein-kinase-dependent and -independent mechanisms in the enteroendocrine STC-1 cell line
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Eric NÉMOZ-GAILLARD, Martine CORDIER-BUSSAT, Chantal FILLOUX, Jean-Claude CUBER, Emmanuel VAN OBBERGHEN, Jean-Alain CHAYVIALLE, Jacques ABELLO; Bombesin stimulates cholecystokinin secretion through mitogen-activated protein-kinase-dependent and -independent mechanisms in the enteroendocrine STC-1 cell line. Biochem J 1 April 1998; 331 (1): 129–135. doi: https://doi.org/10.1042/bj3310129
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