Inositol phosphates and phosphoinositides in rat liver nodules.
Total amounts and turnover rates of phosphoinositides and inositol phosphates in normal rat liver and hepatocyte nodules were investigated. Male Wistar rats were injected i.p. with [3H]inositol 18-20 h before killing. The amount of phosphatidylinositol in a homogenate preparation was roughly doubled in the nodules, though levels of polyphosphoinositides were approximately the same. Basal levels of inositol phosphates were the same in nodules and in normal liver. Turnover rates of inositol tris- and tetrakisphosphates were studied after stimulation of intact cells with vasopressin for different periods of time (0-5 min). The initial rate of formation of inositol trisphosphate after agonist exposure was fast in both nodular and normal cells. Nodular cells reached peak amount of inositol trisphosphate at 2.5-fold basal levels after 20 s, while normal cells peaked after 40 s at 4.5 times the basal amount. The level of inositol tetrakisphosphate was enhanced very quickly in normal cells, but in the nodular cells there was no increase of this inositol phosphate after vasopressin stimulation. To investigate the mechanism of this difference, the activities of inositol 1,4,5-trisphosphate kinase and of inositol 1,4,5-trisphosphate phosphatase were studied. Both activities were rapid and equal in nodules and normal liver. The amount of cell surface receptors for vasopressin was shown to be one-third in the nodules, as compared to normal cells. This quantitative decrease in receptor number was reflected in lower formation of inositol trisphosphate when stimulated with vasopressin, but could not explain the loss of inositol tetrakisphosphate response in nodules. The significance of the reported alterations in second messenger traffic for the growth regulation of nodular cells and for their progression to carcinoma is not yet known, but could add to the nodules being less dependent on growth regulating signals.
Nilsson
H
H
Department of Pathology, Huddinge Hospital, Sweden.
Eriksson
L C
LC
D000818:Animals; D007295:Inositol Phosphates / Q000493:pharmacokinetics*; D000072181:Inositol Polyphosphate 5-Phosphatases; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D010716:Phosphatidylinositols / Q000493:pharmacokinetics*; D010744:Phosphoric Monoester Hydrolases / Q000096:biosynthesis; D010770:Phosphotransferases / Q000096:biosynthesis; D017853:Phosphotransferases (Alcohol Group Acceptor); D011230:Precancerous Conditions / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000032:analysis; D017483:Receptors, Vasopressin
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D010770:Phosphotransferases; D017853:Phosphotransferases (Alcohol Group Acceptor); C051038:Inositol 1,4,5-trisphosphate 3-kinase; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases