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

Abstract

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.

Maintenance of Homeostasis for Thyroid Hormone in the Adult Rat Brain: Possible Involvement of a Nuclear-Mediated Phenomenon

“…This has been supposed to be due to a decreased Na + -K + -ATPase activity during these days. It was observed that the degradation of the acetylcholine receptor was slow in ACT-D-treated muscle culture cells, resulting in a twofold increase in receptor half-life [38]; any change in the rate of AChE secretion was accompanied by an identical change in the rate of acetylcholine receptor incorporation into the plasma membrane [39]. Moreover, increased intracellular cAMP levels, as observed in CHX-plus-PTU-treated rats, may facilitate the release of acetylcholine [40], resulting in an increased activity of AChE to metabolize acetylcholine.…”