Calcium ionophore A23187 inhibits ACTH secretion from a human small cell lung cancer cell line, COR-L103.
The mechanism of ectopic adrenocorticotrophic hormone (ACTH) secretion was examined by studies on the effects of corticotropin-releasing hormone (CRH), dexamethasone, interleukin (IL)-1 beta and 2, somatostatin, calcium ionophore A23187, 12-O-tetradecanoylphorbol-13-acetate (TPA) and 8-bromo-cAMP on pro-opiomelanocortin (POMC) expression and ACTH secretion from a human small cell lung cancer cell line COR-L103. None of these agents except TPA and A23187 had any effect on ACTH secretion from the cell line in short (0-8 hrs) or long term (1-4 days) cultures. In long term cultures, 1-100 nM TPA stimulated ACTH secretion dose-dependently, whereas 500nM A23187 inhibited ACTH secretion completely. When the cells were incubated with 10nM TPA plus 500 nM A23187, the inhibitory action of A23187 on ACTH secretion was suppressed by TPA. These results suggest that the mechanisms of ACTH secretion by COR-L103 cells and normal pituitary cells are different.
First Department of Internal Medicine, School of Medicine, University of Tokushima, Japan.
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Zhang
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Fujinaka
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Yokogoshi
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Saito
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology*; D018288:Carcinoma, Small Cell; D002460:Cell Line; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015592:Immunoradiometric Assay; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007700:Kinetics; D008175:Lung Neoplasms; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis*; D013004:Somatostatin / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D007376:Interleukin-2; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000001:Calcimycin; D013004:Somatostatin; D011333:Pro-Opiomelanocortin; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D013755:Tetradecanoylphorbol Acetate