Effects of lovastatin on adenylyl cyclase activity and G proteins in GH4C1 cells.

We studied the effect of lovastatin, a cholesterol lowering drug, on the basal state of G-proteins in GH4C1 cells. Our data show that the addition of lovastatin markedly decreased the amount of the alpha-subunits of the Gs and Gi-proteins in the plasma membrane. The decrease of alpha s was correlated with a decrease in adenylyl cyclase activity, 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 in the basal state of G-protein in the membrane and consequently on adenylyl cyclase activity.