TY - JOUR
T1 - Regulation of pancreastatin release from a human pancreatic carcinoid cell line in vitro
AU - Jeng, Yow Jiun
AU - Townsend, Courtney M.
AU - Nagasawa, Shingo
AU - Chuo, Shalphen
AU - Kern, Kyle
AU - Yanaihara, Noboru
AU - Ferrar, R. Scott
AU - Hill, Freddie L.C.
AU - Thompson, James C.
AU - Greeley, George H.
PY - 1991/1
Y1 - 1991/1
N2 - 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 mM) and isobutylmethylxanthine (IBMX; 0.01-1.0 mM) 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. Pretreatment of BON cells with monensin, an agent that prevents processing of precursors to smaller peptides, significantly decreased PST, but not CGA, secretion in response to phorbol ester or ionomycin. These findings indicate that protein kinase C, cAMP, and Ca2+ mobilization participate in CGA and PST secretion. Although the observation that secretions of PST and CGA in response to theophylline are quantitatively associated, the absence of a quantitative relationship in the release patterns of PST and CGA in response to phorbol ester and ionomycin do not support a simple precursor-product relationship between CGA and PST. The monensin experiments are consistent with the notion that PST is derived from CGA in BON cells. (Endocrinology 128: 220-225, 1991).
AB - 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 mM) and isobutylmethylxanthine (IBMX; 0.01-1.0 mM) 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. Pretreatment of BON cells with monensin, an agent that prevents processing of precursors to smaller peptides, significantly decreased PST, but not CGA, secretion in response to phorbol ester or ionomycin. These findings indicate that protein kinase C, cAMP, and Ca2+ mobilization participate in CGA and PST secretion. Although the observation that secretions of PST and CGA in response to theophylline are quantitatively associated, the absence of a quantitative relationship in the release patterns of PST and CGA in response to phorbol ester and ionomycin do not support a simple precursor-product relationship between CGA and PST. The monensin experiments are consistent with the notion that PST is derived from CGA in BON cells. (Endocrinology 128: 220-225, 1991).
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U2 - 10.1210/endo-128-1-220
DO - 10.1210/endo-128-1-220
M3 - Article
C2 - 1702700
AN - SCOPUS:0025972331
SN - 0013-7227
VL - 128
SP - 220
EP - 225
JO - Endocrinology
JF - Endocrinology
IS - 1
ER -