Inhibition by phenytoin of in vitro secretion of calcitonin from rat thyroid glands and cultured rat C cells.

Baby rat thyroid glands and cultured rat medullary carcinoma C cells were incubated acutely with phenytoin (38-100 microM), and the calcitonin (CT) secreted into the serum-free medium was measured by radioimmunoassay (RIA). Phenytoin did not alter CT release from glands or C cells incubated in 1 mM Ca, but, when Ca was raised to 1.75 or 2.5 mM, a marked inhibitory effect of phenytoin was apparent. The inhibitory effect could be negated by including 10 microM BAY-K-8644 in the medium. Inhibitory effects on CT release also were obtained with 100 microM trifluoperazine or 100 microM nitrendipine, and these inhibitory effects also were counteracted by 10 microM BAY-K-8644. The results show that clinically relevant amounts of phenytoin can inhibit CT release, perhaps by interfering with C-cell Ca channels or by inhibiting calmodulin-dependent processes.