The calcium-dependent phosphatidylinositol-phosphodiesterase of rat brain. Mechanisms of suppression and stimulation.
1. The activity of the soluble, calcium-dependent phosphatidylinositol-specific phosphodiesterase (EC 3.1.4.10) against [32P]phosphatidylinositol has been investigated. 2. KC1 (only at neutral pH), Mg2+, positively-charged proteins such as histone, and phospholipids containing a choline headgroup are all inhibitory to the enzyme. Choline-phospholipids cause a 90% inhibition at an equimolar ratio to phosphatidylinositol. 3. Other phospholipids (phosphatidylglycerol, phosphatidylserine, phosphatidylethanolamine and phosphatidic acid) are all potent stimulators of the enzyme: maximum stimulation being observed at a ratio of 1 mol activator/5--10 mol phosphatidylinositol. 4. Unsaturated amphiphiles such as oleic and oleoyl alcohol also stimulate the activity, maximum stimulation being observed at about an equimolar ratio to phosphatidylinositol. Saturated amphiphiles (such as stearic acid and stearoyl alcohol) are less effective. 5. The activation by acidic phospholipids and unsaturated amphiphiles appear to be independent as they are additive and, under certain conditions, synergistic. 6. Both types of stimulator (independently or together) can reverse the inhibition caused by histone or phosphatidylcholine. 7. Possible mechanisms of the suppression of the phosphatidylinositol phosphodiesterase in vivo, of its activation, and of the amplification of phosphatidylinositol breakdown are discussed.
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002118:Calcium / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors; D010743:Phospholipids / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D013268:Stimulation, Chemical
D010716:Phosphatidylinositols; D010726:Phosphodiesterase Inhibitors; D010743:Phospholipids; D010727:Phosphoric Diester Hydrolases; D008274:Magnesium; D011188:Potassium; D002118:Calcium