Effect of phenytoin on cytoskeletal protein phosphorylation and neuronal structure in the rat sensory cortex

Phenytoin (PH) is commonly used as an anticonvulsant drug, and it causes several collateral effects including morphological changes in brain cortex neurons and teratogenic lesions in infants of epileptic mothers. Several lines of evidence indicate that PH may exert its action through the modification of phosphorylation patterns of neuronal polypeptides. We have studied the effects of PH on the phosphorylation of cytoskeletal proteins, because this could be relted to the structural modifications induced by PH administration. The dendritic pattern of deep layers of the somatosensory cortex is clearly modified by PH but not the cell number, indicating that the drug disturbs the architecture of the neurons examined. In fact, the pattern of phosphorylation in cytoskeletal extracts of brains of 30‐day‐old rats is changed by PH. In vitro labeling experiments show decrease in the [32P] level of a 43‐kDa polypeptide, whereas 38‐ and 120‐kDa polypeptides show increases in their [32P] contents. The 43‐kDa polypeptide has been identified as actin by in vitro experiments using a novel approach to determine cytoskeletal poypeptide behvior. We conclude that PH affects the posttranslational phosphorylation of actin and other related cytoskeletal proteins and in this manner may alter the normal morphological layout of dendritic patterns in the somatosensory cortex.