Enhanced inositide turnover in brain during bicuculline-induced status epilepticus

Because brain inositides are enriched in the 1-stearoyl-2-arachidonoyl species, they form a likely source for the tetraenoic free fatty acids (FFA) and diacylglycerols (DG) that are accumulated during seizures. To study inositide turnover during bicuculline-induced seizures, rats were injected intraventricularly and bilaterally with 10–20 μCi 32P, mechanically ventilated and sacrificed by 6.5 KW head-focused microwave irradiation. Seizure activity was recorded by electroencephalography. Bicuculline-induced seizure activity resulted in: a) almost 50% increase in 32P labeling of phosphatidic acid (PA); phosphatidylinositol (PI) and phosphatidylinositol 4,5-bisphosphate (PIP 2) also increased (24% and 36%, respectively); b) no change in other lipids; and c) water-soluble phosphodiesteratic degradation products, analyzed by high voltage paper electrophoresis, increased 24% in the amount of radiotracer recovered as inositol 1,4-bisphosphate (IP 2) and by 44% in the amount recovered as inositol 1,4,5-trisphosphate (IP 3). These data indicate that during experimental status epilepticus the cerebral inositide cycle is accelerated: PIP 2 → ( (IP 3 → IP 2 → IP → I) + DG → PA → PI → PIP → PIP 2.