Lovastatin is a potent inhibitor of cholecystokinin secretion in endocrinetumor cells in culture

Lovastatin prevents isoprene synthesis thereby affecting the structural org anization of proteins involved in protein transport and secretion. Lovastat in at 1 mu M decreases CCK 8 secretion by over 50% in WE cells and in CCK 8 expressing AtT20 cells. At 10 mu M CCK 8 secretion was inhibited by two th irds and at 100 mu M, cytotoxic effects were observed in both cell types. A ddition of mevalonate does not restore CCK secretion and stimulation of sec retion by forskolin is also partially inhibited. Cellular content of CCK 8 and pro-CCK were not altered in either of these cell lines except at 100 mu M lovastatin. Our results clearly demonstrate that lovastatin at 1 mu M st rongly inhibits CCK 8 secretion at multiple levels while having little or n o effect on its synthesis. This effect on secretion may be partly responsib le for the adverse gastrointestinal side effects of lovastatin in patients. (C) 2000 Elsevier Science Inc. All rights reserved.