Alteration of acetylcholine receptor and acetylcholinesterase metabolism by actinomycin D in cultured muscle cells.

Actinomycin D (ACT-D), an inhibitor of transcription, was added to chick muscle cultures to study its effect on the synthesis of acetylcholine receptor (ACHR) and acetylcholinesterase (ACHE, EC 3.1.1.7). Doses of ACT-D (1.85-18.5 nM), which inhibited uridine incorporation up to 80%, increased ACHR, ACHE, and creatine kinase (CK, EC 2.7.3.2) levels without affecting general cell protein. Degradation of ACHR was slower in ACT-D treated cultures than controls, resulting in a twofold increase in receptor half-life. Uridine incorporation was inhibited by ACT-D in both mononucleated cells and myotubes and [3H]uridine nuclear grain distribution were shifted to values lower than controls. The results indicate that posttranscriptional effects of ACT-D increase levels of ACHR, ACHE, and CK and that decreased degradation could account for the increase in the number of surface ACH receptors.