Ethanol effects on rat brain phosphoinositide metabolism

An increase in acidic phospholipids in brain plasma and synaptic plasma membranes upon chronic ethanol administration was observed. Chronic ethanol administration resulted in an increase in 32Pi incorporation into the acidic phospholipids in synaptosomes. Postdecapitative ischemic treatment resulted rapid degradation of poly-PI in rat brain. However, there was a rapid appearance of IP2 in ethanol group which indicated a more rapid turnover of IP3 in the ethanol-treated rats. Carbachol stimulated accumulation of labeled inositol phosphates in brain slices and synaptosomes. Carbachol-stimulated release of IP and IP2 was calcium dependent and was inhibited by EGTA and atropine. Adenosine triphosphates and 1 mM further enhanced carbachol-induced formation of IP and IP2, but showed an increase and a decrease in IP3 at 1 mM and 0.01 mM, respectively. Guanosine triphosphate at 0.1 mM did not change in labeled IP, but there was a significant increase in labeled IP2 and decrease in IP3. Mn and CMP greatly enhanced incorporation of [3H]-inositol into PI, but not into poly-PI labeling in brain synaptosomes. Incubation of brain synaptosomes resulted in a Ca2+, time-dependent release of labeled IP. However, the pool of PI labeled through this pathway is not susceptible to carbachol stimulation. When saponin permeabilized synaptosomal preparations were incubated with [3H]-inositol-PI or [14C]-arachidonoyl-PI, ATP enhanced the formation of labeled IP and DG