Evidence That Inositol 1-phosphate in Brain of Lithium-Treated Rats Results Mainly From Phosphatidylinositol Metabolism

Biochem J. 1987 Mar 1;242(2):517-24. doi: 10.1042/bj2420517.

Abstract

In cerebral cortex of rats treated with increasing doses of LiCl, the relative concentrations of Ins(1)P, Ins(4)P and Ins(5)P (when InsP is a myo-inositol phosphate) are approx. 10:1:0.2 at all doses. In rats treated with LiCl followed by increasing doses of pilocarpine a similar relationship occurs. myo-Inositol-1-phosphatase (InsP1ase) from bovine brain hydrolyses Ins(1)P, Ins(4)P and Ins(5)P at comparable rates, and these substrates have similar Km values. The hydrolysis of Ins(4)P is inhibited by Li+ to a greater degree than is hydrolysis of Ins(1)P and Ins(5)P. D-Ins(1,4,5)P3 and D-Ins(1,4)P2 are neither substrates nor inhibitors of InsP1ase. A dialysed high-speed supernatant of rat brain showed a greater rate of hydrolysis of Ins(1)P than of D-Ins(1,4)P2 and a lower sensitivity of the bisphosphate hydrolysis to LiCl, as compared with the monophosphate. That enzyme preparation produced Ins(4)P at a greater rate than Ins(1)P when D-Ins(1,4)P2 was the substrate. The amount of D-Ins(3)P [i.e. L-Ins(1)P, possibly from D-Ins(1,3,4)P3] is only 11% of that of D-Ins(1)P on stimulation with pilocarpine in the presence of Li+. DL-Ins(1,4)P2 was hydrolysed by InsP1ase to the extent of about 50%; both Ins(4)P and Ins(1)P are products, the former being produced more rapidly than the latter; apparently L-Ins(1,4)P2 is a substrate for InsP1ase. Li+, but not Ins(2)P, inhibited the hydrolysis of L-Ins(1,4)P2. The following were neither substrates nor inhibitors of InsP1ase; Ins(1,6)P2, Ins(1,2)P2, Ins(1,2,5,6)P4, Ins(1,2,4,5,6)P5, Ins(1,3,4,5,6)P5 and phytic acid. myo-Inositol 1,2-cyclic phosphate was neither substrate nor inhibitor of InsP1ase. We conclude that the 10-fold greater tissue contents of Ins(1)P relative to Ins(4)P in both stimulated and non-stimulated rat brain in vivo are the consequence of a much larger amount of PtdIns metabolism than polyphosphoinositide metabolism under these conditions.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cattle
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism*
  • Chlorides / pharmacology*
  • Dose-Response Relationship, Drug
  • Hydrolysis
  • In Vitro Techniques
  • Inositol Phosphates / metabolism*
  • Kinetics
  • Lithium / pharmacology*
  • Lithium Chloride
  • Phosphatidylinositols / metabolism*
  • Phosphoric Monoester Hydrolases / metabolism
  • Pilocarpine / pharmacology
  • Sugar Phosphates / metabolism*

Substances

  • Chlorides
  • Inositol Phosphates
  • Phosphatidylinositols
  • Sugar Phosphates
  • Pilocarpine
  • Lithium
  • Phosphoric Monoester Hydrolases
  • myo-inositol-1 (or 4)-monophosphatase
  • Lithium Chloride