The cytochalasins (CE, CD, CB and H,CB) inhibit numerous cellular processes which require the interaction of actin with other structural and contractile proteins. In this report we describe the effects of the cytochalasins on the viscosity and morphology of muscle and platelet actin. The cytochalasins decreased the viscosity of F-actin solutions. The effect of H,CB, CB and CD on F-actin viscosity was maximal at concentrations of 20-50pM and did not increase with time. In contrast, CE caused a progressive decrease in the viscosity of F-actin solutions which was dependent upon the concentration of CE and the duration of incubation of the CE-actin mixture, After two hours of incubation of drug-actin mixtures, the relative effectiveness of the cytochalasins in reducing the viscosity of F-actin was CE>CD>CB=H2CB. The effects of CD and CE were paralleled by morphologic changes in negatively stained actin filaments. The effects of the cytochalasins on the viscosity and morphology of muscle and platelet actin were the same whether the drugs were added before or after the polymerization of the protein.
highly specific. Because the relative potencies of these drugs for affecting motile processes and the relative affinities of the drugs for binding sites within a variety of cells are CE>CD>CB=H,CB, the effects of cytochalasins on actin described here may contribute t o some of the biological effects of the drugs on motile processes.
These studies show that the interaction of the cytochalasins with actin is
Key words: cytochalasins, muscle and platelet actin, microfilaments. cell motility, viscosity changes, electron microscopy
The cytochalasins, a family of alkaloids produced by a variety of fungi, have been found t o inhibit a large number of cellular processes which are thought t o involve interactions of contractile proteins (for review, see [ 11 ). Studies utilizing electron microscopy and immunofluorescence techniques showed that treatment of cultured mammalian cells with cytochalasin B (CB), by far the most studied congener, results in transformation of actin-containing microfilaments in the cells into amorphous clumps of filamentous materials [eg, 2 , 31. These observations directed the subsequent search for the site of