Regulation of Pancreastatin Release from a Human Pancreatic Carcinoid Cell Line in Vitro

The objective of these experiments was to investigate the influence of activation of three second messenger systems (protein kinase-C, adenylate cyclase-cAMP, and calcium mobilization) on the secretion of pancreastatin (PST) and chromogranin-A (CGA) by a human pancreatic carcinoid cell line (BON) in tissue culture. Stimulation of protein kinase-C by a phorbol ester (0.025–7.5 μM) caused a significant dose-related release of PST (186 ± 22-4271 ± 228% over controls). Treatment of BON cells with graded doses of 8-bromo-cAMP (0.14-3.0 mMJ and isobutylmethylxanthine (IBMX; 0.01-1.0 DIM) also stimulated a dose-related release of PST (107 ± 22-284 ± 28 and 16 ± 12-1076 ± 100% over controls, respectively). Incubation of BON cells with ionomycin (0.134–13.4 μM) increased the release of PST (102 ± 15-554 ± 21% over controls) in a dose-related manner. A combination of IBMX and ionomycin resulted in an additive effect, whereas treatment with a phorbol ester plus IBMX resulted in a synergistic effect on PST release. P...