Identification of cytidine diphosphate-diglyceride in the pineal gland of the rat and its accumulation in the presence of DL-propranolol.

CDP-diglyceride, an important metabolic intermediate in the biosynthesis of phospholipids, has been isolated for the first time from a mammalian tissue. The isolated material, labeled in incubations of intact rat pineal glands with 32P, [3H]cytidine, or [3H]CTP in the presence of DL-propranolol, was chromatographically identical with authentic CDP-diglyceride and was able to serve as phosphatidyl donor in the enzymatic synthesis of phosphatidylinositol and phosphatidyglycerol. It yielded the expected products upon enzymatic and chemical degradation. No dCDP-diglyceride was detected No radioactive CDP-diglyceride was detected following incubations in the absence of propranolol. Stimulation of CDP-diglyceride labeling from 32P1 occurred at propranolol concentrations between 0.03 and 1.0 mM. Net synthesis of the liponucleotide was shown. At 0.1 mM, propranolol incrased the incorporation of radioactivity into phosphatidylglycerol, phosphatidylinositol, and phosphatidic acid. When inositol (10 mM) and propranolol (0.1 mM) were both present, phosphatidylinositol labeling was further increased, wheas stimulation of phosphatidylglycerol and CPD-diglyceride labeling was abolished. Since CDP-diglyceride did not accumulate in the absence of the drug, its availability may normally be the limiting factor in phosphatidylinositol and phosphatidylglycerol biosynthesis. When propranol is present, inositol may become limiting and thus may lead to the observed labeling pattern.