Studies on the effects of acetylcholine and antiepileptic drugs on 32PI incorporation into phospholipids of rat brain synaptosomes.

Studies were conducted on the effects of antiepileptic drugs on the acetylcholine-stimulated 32P labeling of phospholipids in rat brain synaptosomes. Of the four antiepileptic drugs investigated in the present study, namely phenytoin, carbamazepine, phenobarbital, and valproate, only phenytoin blocked the acetylcholine-stimulated 32P labeling of phosphatidylinositol and phosphatidic acid, and the acetylcholine-stimulated breakdown of polyphosphoinositides. Phenytoin alone, like atropine alone, had no effect on the 32P labeling of phospholipids nor on the specific radioactivity of [32P]ATP. Omission of Na+ drastically reduced both the 32P labeling of synaptosomal phospholipids and the specific radioactivity of [32P]ATP and furthermore it significantly decreased the phosphoinositide effect. It was concluded that certain antiepileptic drugs, such as phenytoin, could exert their pharmacological actions through their antimuscarinic effects. In addition the finding that phenytoin, which acts to regulate NA+ and Ca2+ permeability of neuronal membranes, also inhibited the phosphoinositide effects in synaptosomes, support the conclusions that Ca2+ and Na+ are probably involved in the molecular mechanism underlying this phenomenon in excitable tissues.U