cytochalasin-d and chaetoglobosins

The ability of cytochalasin to alter phosphoinositide metabolism was evaluated in naive, murine splenic B lymphocytes. The generation of total inositol phosphates was stimulated by treatment with cytochalasin D, as was the generation of inositol trisphosphate. The cytochalasin-induced increase in inositol phosphates appeared to depend on interaction with actin, and it was inhibited by phorbol esters. Inositol phosphate production was not stimulated in splenic T lymphocytes. The results suggest that the previously observed increase in intracellular calcium produced by cytochalasin is part of a more generalized signaling event that includes phosphoinositide turnover, and, further, raise the possibility of a functional association between actin and phospholipase C.

Topics: Actins; Animals; B-Lymphocytes; Cytochalasin D; Cytochalasins; Indole Alkaloids; Indoles; Mice; Mice, Inbred A; Phorbol Esters; Phosphatidylinositols; T-Lymphocytes

It was shown that substoichiometric concentrations of chaetoglobosin J, one of the fungal metabolites belonging to cytochalasins, inhibited the elongation at the barbed end of an actin filament. Stoichiometric concentrations of chaetoglobosin J decreased both the rate and the extent of actin polymerization in the presence of 75 mM KCl, 0.2 mM ATP and 10 mM Tris-HCl buffer at pH 8.0 and 25 degrees C. In contrast, stoichiometric concentrations of cytochalasin D accelerated actin polymerization. Chaetoglobosin J slowly depolymerized F-actin to G-actin until an equilibrium was reached. Analyses by a number of different methods showed the increase of monomer concentration at equilibrium to depend on chaetoglobosin J concentrations. F-actin under the influence of stoichiometric concentrations of chaetoglobosin J only slightly activated the Mg2+-enhanced ATPase activity of myosin at low ionic strength. It is suggested that when the structure of the chaetoglobosin-affected actin filaments is modified, the equilibrium is shifted to the monomer side, and the interaction with myosin is weakened.

Topics: Actins; Animals; Cytochalasin D; Cytochalasins; Indole Alkaloids; Indoles; Kinetics; Macromolecular Substances; Muscles; Mycotoxins; Rabbits; Structure-Activity Relationship