Early changes of liver phospholipase C activity in rats fed an orotic acid supplemented diet

In this study of the effect of an orotic-acid (O.A.) diet on the activity of membrane-bound phosphoinositide-specific phospholipase C (PL-C) of rat liver, its enzymatic activity was evaluated in vitro on membranes obtained from the hepatic tissue of male Wistar rats fed a diet containing 1% O.A. for 2 and 5 days and from control rats. The rate of breakdown of labelled phosphatidylinositol-4,5-bisphosphate (Ptdins-P2) added to the isolated membranes was measured both in the absence and in the presence of guanosine-5'-O-thiotriphosphate (GTP gamma S). The enzyme stimulation by bombesin was also analysed. PL-C activity proved to be deeply and early modified by O.A. The basal activity was increased 2 days after feeding on the O.A.-supplemented diet, but the difference from control rats was no more significant after 5 days of this diet. The most interesting changes concerned the response to bombesin; the hormone failed to induce any stimulation of PL-C in O.A.-treated rats after either 2 or 5 days of diet, whereas it nearly doubled Ptdins-P2 breakdown in the liver membranes from control rats. The lack of any stimulation of the phospholipase C by bombesin in O.A.-treated rats indicates a deep impairment of this signal transmission system; its possible causes and consequences are discussed.