Proliferative response to phenytoin and nifedipine in gingival fibroblasts cultured from humans with gingival fibromatosis

The response of gingival fibroblasts cultured from humans with gingival fibromatosis to phenytoin (PHT) and nifedipine (NIF) was investigated. PHT and NIF induced proliferation, and increased the expression of immunoreactive endothelin-1 (ET-1). ET-1 (0.1 nm-1 mum) itself also induced proliferation in a concentration-dependent manner. The proliferation was inhibited by BQ-123 (ETA receptor antagonist; 1 mum) and TAK044 (ETLambda/ETB, receptor antagonist; 1 mum), but not by BQ-788 (ETB receptor antagonist: 1 mum). The proliferation induced by PHT (0.25 mum) and NIF (0.25 mum) was inhibited by BQ-123 (1 mum). In addition, the results of Western blot analysis indicated the presence of ETA and ETB receptors in/on the fibroblasts. These findings suggest that PHT- and NIF-induced gingival proliferation may be mediated by endogenously generated ET-1, possibly via ETA receptors.