MODULATION OF CCK MESSENGER-RNA IN CELL-LINES IN RESPONSE TO ISOPROTERENOL AND RETINOIC ACID

Regulation of cholecystokinin (CCK) expression was studied in the huma n neuroepithelioma cell line SK-N-MCIXC and the rat medullary thyroid carcinoma cell line WE 4/2. The cells were treated with the P-adrenerg ic agonist isoproterenol and retinoic acid, a natural derivative of vi tamin A, which plays a role in cell growth and proliferation. Levels o f CCK mRNA were determined after 6, 12 and 24 h drug treatments, with Northern blot analysis using human CCK riboprobes. In WE 4/2 cells no differences were observed in CCK mRNA levels, between control and isop roterenol treated cells, after 6, 12 or 24 h treatments. In SK-N-MCIXC cells isoproterenol increased CCK mRNA levels at all time points exam ined, the beta-adrenergic antagonist propranolol blocked this effect. SK-N-MCIXC cells were also treated with actinomycin D or cycloheximide in combination with isoproterenol. Actinomycin D decreased CCK mRNA l evels. Cycloheximide increased CCK mRNA levels when compared to isopro terenol acting alone. Retinoic acid did not affect CCK mRNA levels in WE 4/2 cells. In SK-N-MCIXC cells, retinoic acid consistently decrease d CCK mRNA level. CCK mRNA levels in SK-N-MCIXC cells treated with ret inoic acid combined with either isoproterenol or phorbol-12-myristate- 13 acetate, were not significantly different from cells treated with r etinoic acid alone.