Observations on the Mechanism of Emetine Poisoning of Myocardial Tissue

Abstract

The effect of emetine hydrochloride on protein synthesis in rat myocardium was studied. Emetine inhibited incorporation of tritiated leucine into soluble proteins and actomyosin in an in vitro system using minced rat myocardium in a supporting medium. Fifty percent inhibition of incorporation of the isotope into soluble proteins and actomyosin occurred at an emetine concentration of 5 X 10~7 M. Incorporation was also significantly inhibited when animals were treated with emetine for three days. The data suggest that emetine toxicity in the myocardium may be mediated through its effects on protein biosynthesis.

Protein Synthesis in the Myocardiopathy and Muscular Dystrophy of the Syrian Hamster

“…Immediately after decapitation the heart, diaphragm and biceps femoris were removed and placed in ice-cold 0.1 M KCl, pH 7.4 (Beller, 1968;Beller & Mongillo, 1969) which was gassed with 95% 0, and 5% CO,. Heart muscle slices, hemidiaphragms and biceps femoris muscle strips were found to give the best results of several tissue preparations tested.…”

“…The myocardial tissue was then homogenized and the proteins soluble at low ionic strength were extracted in a phosphate buffer (pH 7.4) containing 0.1 M KCl according to the method described by Beller (1968). The tissue remaining after removal of the soluble protein fraction was extracted for actomyosin according to the method of Inchiosa (1964).…”

Inhibition of Incorporation of Leucine into Myocardial Proteins of the Rat by Antiarrhythmic Agents

“…A detailed description of the methods employed in this study has been published (1). Rat hearts were exposed in vitro to each agent by incubating increasing concentrations of each drug in 0.1 ml of deionized water or the appropriate solvent with uniform particles of rat myocardium prepared from Sprague-Dawley rats weighing 100 to 150 g. These particles were suspended in 9.8 ml of minimal essential tissue culture medium (3) prepared without leucine and incubated at 39°C for 15 minutes.…”

“…Both protein extracts were purified by methods previously described (1,4,5), and aliquots were taken for determination of protein content by the Lowry method (6). Radioactivity was determined in a Packard liquid scintillation counter, using a thixotropic gel for suspension of the proteins (1, 7).…”

“…• In an earlier communication, we described the inhibition by emetine hydrochloride of the incorporation of tritiated leucine into myocardial proteins (1). Emetine was studied because of reported cardiac toxicity with myocardial depression and because evidence for inhibition of protein synthesis by the alkaloid in cell cultures, plants, and yeast had previously been presented by Grollman (2).…”