Lovastatin is a potent inhibitor of cholecystokinin secretion in endocrine tumor cells in culture.
Lovastatin prevents isoprene synthesis thereby affecting the structural organization of proteins involved in protein transport and secretion. Lovastatin at 1 microM decreases CCK 8 secretion by over 50% in WE cells and in CCK 8 expressing AtT20 cells. At 10 microM CCK 8 secretion was inhibited by two thirds and at 100 microM, cytotoxic effects were observed in both cell types. Addition of mevalonate does not restore CCK secretion and stimulation of secretion 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 microM lovastatin. Our results clearly demonstrate that lovastatin at 1 microM strongly inhibits CCK 8 secretion at multiple levels while having little or no effect on its synthesis. This effect on secretion may be partly responsible for the adverse gastrointestinal side effects of lovastatin in patients.
Vishnuvardhan
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Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.
Beinfeld
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MC
D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D004701:Endocrine Gland Neoplasms; D008148:Lovastatin / Q000494:pharmacology*; D008798:Mevalonic Acid / Q000494:pharmacology; D051379:Mice; D051381:Rats; D012844:Sincalide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D005576:Colforsin; D008148:Lovastatin; D012844:Sincalide; D008798:Mevalonic Acid