Stimulation of free fatty acid and diacylglycerol accumulation in cerebrum and cerebellum during bicuculline-induced status epilepticus. Effect of pretreatment with alpha-methyl-p-tyrosine and p-chlorophenylalamine.
The pool size and composition of free fatty acids (FFA) and diglycerides (DG) from the cerebrum and cerebellum of rats undergoing bicuculline-induced seizures were studied. A fourfold increase in cerebral FFA occurred 3-4 min after bicuculline injection; arachidonic and stearic acids were the principal fatty acids accumulated. Cerebellar FFA also increased, but to a lesser extent. An increased production of arachidonic acid took place in the cerebrum as a function of time after bicuculline injection. Other fatty acids produced were oleic, palmitic, and docosahexaenoic acids. A twofold increase in cerebral arachidonic acid was seen at the time of the first generalized tonic-clonic convulsion. However, a 13- to 17-fold increase in arachidonic acid was seen approximately 5-6 min after bicuculline injection. The rise in other FFA was much smaller. Stearoyl- and arachidonoyl-DG were also accumulated. The drug alpha-methyl-p-tyrosine was found to (a) potentiate the bicuculline-stimulated release of cerebellar FFA, and (b) inhibit by 70% the production of stearoyl- and arachidonoyl-DG in the cerebrum and cerebellum. Basal production of FFA was stimulated by p-chlorophenylalanine, but the drug had no effect on the bicuculline-induced changes. Hydrolysis of phospholipids enriched in stearoyl-arachidonoyl groups, such as phosphatidylinositol of excitable membranes, may be stimulated during seizures.
D000818:Animals; D001640:Bicuculline; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005260:Female; D010134:Fenclonine / Q000494:pharmacology*; D005989:Glycerides / Q000378:metabolism*; D007700:Kinetics; D008781:Methyltyrosines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism*; D019805:alpha-Methyltyrosine
D004075:Diglycerides; D005230:Fatty Acids, Nonesterified; D005989:Glycerides; D008781:Methyltyrosines; D019805:alpha-Methyltyrosine; D010134:Fenclonine; D001640:Bicuculline