Effects of phenytoin on acetylcholinesterase activity and cell protein in cultured chick embryonic skeletal muscle

Abstract

Cultured pectoral muscle from 11-day-old chick embryos was treated for 48 h with phenytoin (diphenylhydantoin, DPH) in concentrations ranging from 15 to 270 μg/ml on days 7–9 in vitro. Acetylcholinesterase (AChE, EC 3.1.1.7), creatine phosphokinase (CPK, EC 2.7.3.2), and lactic dehydrogenase (LDH, EC 1.1.1.27) activities, [³H]leucine incorporation into protein, and total protein of the cultures decreased in a dose-related manner with DPH concentrations of 30 μg/ml and greater. Total AChE activity and AChE activity released into the medium were specifically decreased with 15 μg DPH per millilitre. In cultures treated chronically with 15 μg DPH per millilitre on days 5–13 in vitro, total AChE activity and AChE activity released into the medium were 66.0 ± 13.2 and 64.7 ± 11.8% of untreated controls, respectively, but cellular AChE activity, cell protein, and [³H]leucine incorporation into protein were unaffected. The results indicate that DPH specifically decreases the total net synthesis of AChE activity by a direct action on cultured chick embryo muscle.