Arachidonic acid, stearic acid, and diacylglycerol accumulation correlates with the loss of phosphatidylinositol 4,5-bisphosphate in cerebrum 2 seconds after electroconvulsive shock: Complete reversion of changes 5 minutes after stimulation

Abstract

The effects of electroconvulsive shock (750 msec, 130 V, 150 pps) on the endogenous content of rat cerebral lipids were studied 2, 5, 10, 20, 30, 60, and 300 sec after stimulation. Rapid enzyme inactivation in situ was attained by high-power head-focused microwave irradiation (6.5 kW, 2450 MHz). At 10 sec, phosphatidylinositol 4,5-bisphosphate (PIP₂) mass had decreased by 249 nmol per g wet wt, mainly due to loss of arachidonate and stearate. At the same time, the stearoyl-arachidonoyl glycerol accumulated, although to a lesser extent than the loss exhibited in PIP₂. Changes in phosphatidylinositol and in phosphatidylinositol 4-phosphate mass were not statistically significant. Free fatty acids and diacylglycerold accumulated to 395 nmol per g wet wt; arachidonic and stearic acids composed 322 nmol of these lipids. Hence, the reduction in content PIP₂ is sufficient to account 80% of the increases in free fatty acid and diacylglycerol mass. Thirty-three and 12 nmol of accumulated free palmitic and scosahexaenoic acids, respectively, are not accounted for by the loss of PIP₂. Sixty seconds after stimulation, PIP₂ content returned to 90% of control levels, while diacylglycerol tended to remain below control levels. Free fatty acids had not returned to control levels by 60 sec, with the exception of docosahexaenoic acid. At 300 sec, PIP₂, diacylglycerol, and free fatty acids had all returned to control levels. It is proposed that the elctroshock-induced release of neurotransmitters is associated with stimulation of phospholipases A₁ and A₂ at the presynaptic membrane followed by receptor-linked phosphodiesteratic cleavage of PIP₂ at the postsynaptic membrane, and that Ca²⁺ influx resulting from membrane depolarization activates the deacylation of stearoyl-arachiodonoyl glycerol.