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 hor mone (CRH), dexamethesone, interleukin (IL) -1 beta and 2, somatostati n, 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 secretio n from the cell line in short (0-8 hrs) or long term (1-4 days) cultur es. In long term cultures, 1-100 nM TPA stimulated ACTH secretion dose - dependently, whereas 500nM A23187 inhibited ACTH secretion completel y. 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-L10 3 cells and normal pituitary cells are different. (C) 1995 Academic Pr ess, Inc.