REGULATION OF THE LEVEL OF ENDOGENOUS PHOSPHORYLATION OF SPECIFIC BRAIN PROTEINS BY DIPHENYLHYDANTOIN1

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Abstract
—: Diphenylhydantoin (DPH) in therapeutic concentrations caused a decrease in the net level of endogenous phosphorylation of two specific proteins from rat brain cerebri, while not significantly affecting the phosphorylation of other protein substrates. The apparent molecular weights of the DPH‐ specific substrate proteins were 60‐63,000 and 49‐52,000, and were designated proteins DPH‐L and DPH‐M, respectively. DPH decreased both the initial rate and the net level of [32P] phosphate incorporation from [γ‐32P] ATP into proteins DPH‐L and DPH‐M. The concentrations of DPH required to produce a half maximal decrease in the levels of phosphorylation of proteins DPH‐L and DPH‐M was 3 × 10‐4 and 8 × 10 ‐4 M, respectively. The effects of DPH on the incorporation of [32P] phosphate into these specific brain proteins were independent of the concentration of ATP over a wide range of ATP concentrations. The DPH‐specific proteins were demonstrated to be present in synaptosomal preparations. The results are compatible with the hypothesis that some of the stabilizing actions of DPH on neuronal tissue and seizure discharge may be mediated by the effect of this anticonvulsant on the phosphorylation of specific brain protein substrates.