EFFECTS OF LOVASTATIN ON ADENYLYL-CYCLASE ACTIVITY AND G-PROTEINS IN GH(4)C(1) CELLS

We studied the effect of lovastatin, a cholesterol lowering drug, on t he basal state of G-proteins in GH(4)C(1) cells, Our data show that th e addition of lovastatin markedly decreased the amount of the alpha-su bunits of the G(s) and G(i)-proteins in the plasma membrane, The decre ase of alpha s was correlated with a decrease in adenylyl cyclase acti vity, and both effects were reverted by the presence of mevalonate. As the attachment of G protein subunits to the membrane is dependent on gamma-subunit prenylation, we assume that the mechanism through which lovastatin exerts its effects on G-proteins is the lack of mevalonate for the synthesis of prenyl residues, In conclusion, our data indicate that some of the effects of lovastatin are mediated through changes i n the basal state of G-protein in the membrane and consequently on ade nylyl cyclase activity.