The inhibition and activation of Ca2+-dependent phosphatidylinositol phosphodiesterase by phospholipids and blood plasma.
1. Phosphatidylinositol-phosphodiesterase (EC 3.1.4.10) was strongly inhibited when ovophosphatidylcholine and saturated phosphatidylcholines with acyl chain lengths of more than eight carbon atoms were mixed with its substrate. In contrast, dihexanoylglycerophosphocholine produces a marked activation attended by a breakdown of the bilayer structure of the substrate. 2. C12, C14, and C16 lysophosphatidylcholines gave a progressive inhibition of the enzyme with increasing chain length; C10 lysophosphatidylcholine activated the reaction. 3. The enzyme was strongly inhibited by blood plasma and serum and by blood lipoproteins. 4. Phosphatidic acid, and certain lysophosphatidic acids (oleoyl and palmitoylglycerophosphates) activated the hydrolysis at a physiological pH, whereas decanoylglycerophosphate had little effect. 5. Phosphatidic acid at a concentration of 1% molar total lipid P produced an enhancement of the hydrolysis of the phosphatidylinositol substrate contained in a lipid environment which approximated to the inner (cytoplasmic) lamella of the plasma membrane bilayer of the liver sinusoidal cell surface. 6. The possible role of phospholipid molecules adjacent to phosphatidylinositol in controlling the hydrolysis of the latter in the proximity of a cell surface receptor is discussed. It is suggested that phosphatidic acid formed by the action of diacylglycerol kinase could amplify any increased hydrolysis of phosphatidylinositol which results from stimulation of the cell by an agonist.
D000818:Animals; D001769:Blood; D002118:Calcium / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D010712:Phosphatidic Acids / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000494:pharmacology; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010716:Phosphatidylinositols / Q000037:antagonists & inhibitors / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors; D010743:Phospholipids / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D051381:Rats; D012756:Sheep
D008074:Lipoproteins; D008244:Lysophosphatidylcholines; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D010716:Phosphatidylinositols; D010726:Phosphodiesterase Inhibitors; D010743:Phospholipids; D010727:Phosphoric Diester Hydrolases; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D002118:Calcium