Abstract
Both phenytoin (PHT) and glucocorticoid (GC) have been reported to be an effective teratogen for the production of cleft palate. The authors suggest the possibility that a part of GC-receptor to which PHT competitively bind (common receptor with PHT), participate in the production of cleft palate. In the present study, as one of the studies for the elucidation of the mechanism of cleft palate induction with PHT, we investigated the PHT-receptors and its relation with GC in the lung tissue of mice, which were either sensitive (CF1) or resistant (C57BL/6) to PHT or GC. Scatchard analysis of the specific binding of 14C-PHT to the cytosol protein revealed that the total capacity of PHT-receptor for CF1 (1, 571 fmole/mg protein) was much greater than that for C57BL/6 (994fmole/mg). The value of the Kd's for these strains, however, were 18.1 and 16.5 nM, respectively, indicating the absence of any great difference between both strains. The capacity of the common receptors with GC for CF1 (236 fmole/mg) was greater than that for C57BL/6 (126fmole/mg). But, the value of the Kd's for these strains were 5.4 and 3.1 nM, respectively, indicating the absence of a great difference between the strains. The analysis indicated that the lung tissue cytosols of both strains also contain the proper receptor for PHT, which is in a much greater amount than that of the common receptor. The results obtained in the present study suggest that, although there might exist a common pathway in the induction of cleft palate with PHT and GC including a common receptor for PHT and GC, the induction mechanisms are not exactly the same. The function and role of the proper receptors for PHT in the production of cleft palate need further examination.
