CHARACTERIZATION OF THE RELEASE OF CHOLECYSTOKININ FROM A MURINE NEUROENDOCRINE TUMOR-CELL LINE, STC-1

The murine neuroendocrine cell line, STC-1, was found to contain 296.8 +/- 1.8 fmol of cholecystokinin-like immunoreactivity (CCK-LI) per mg cell protein. Immunocytochemical stain of STG-1 cells maintained in m onolayer culture indicated that CCK-LI activity was present in 93% of the cells. Analysis by reverse-phase high-performance liquid chromatog raphy indicated that STC-1 cells contained CCK-8 and an unidentified f orm as the predominant storage form. However, only CCK-8 was released into the culture medium upon stimulation by various secretagogues. The release of CCK-LI from STC-1 cells was stimulated by dibutyryl cAMP, forskolin, KCI, A23187, 4 beta-phorbol 12-myristate 13-acetate and lum inal stimulants, e.g., sodium oleate, L-tryptophan, camostat and plaun otol. The release of CCK-LI from STC-1 cells was also stimulated by a neuropeptide, bombesin. The stimulatory effects of most of these agent s were dose dependent. The stimulatory effects of dibutyryl cAMP, fors kolin, and plaunotol were potentiated by 3-isobutyl-1-methyl xanthine, while that of camostat was not. The results obtained in this study in dicate that the release of CCK from STC-1 cells shares the same charac teristics of CCK release as from the CCK-secreting cells of the intest inal mucosa observed both in the dog and the rat in vitro and in vivo. Thus, the cellular mechanism of CCK release which appears to be cAMP- and Ca2+-dependent may be modulated by cellular protein kinase C acti vity. The STC-1 cell appears to be a suitable model for studying the m echanism of CCK release.