What we have learned from phalloidin

Changes in the Localization of the Rat Canalicular Conjugate Export Pump Mrp2 in Phalloidin–Induced Cholestasis

“…42,43 Phalloidin-induced changes involve actin aggregation, 35,44 alteration of the pericanalicular actomyosin complex, 40,45 and displacement of the subplasmalemmal microfilaments. 35 This leaves domains of the cell membrane partly separated from the normal microfilament web 2,40 and leads to gaps in the cortical actin ring. Alteration of pericanalicular actin organization inhibits canalicular contraction 32 but by itself does not necessarily affect the function of canalicular export pumps.…”

“…12,[32][33][34] Agents interfering with microfilaments, such as phalloidin and cytochalasins, impair canalicular motility, and result in cholestasis. [2][3][4]10,32 However, altered actin organization per se does not impair the secretion of substrates for the bile salt export pump and for Mrp2 in isolated rat hepatocyte couplets. 9 We therefore hypothesized that changes in actin filament organization would rather alter the localization and distribution of canalicular transport proteins as shown in other forms of intrahepatic cholestasis.…”

“…1 Cholestasis is among the earliest effects of acute phalloidin poisoning 2,3 and has been extensively studied in rats. [3][4][5][6][7] Phalloidin-induced cholestasis involves impaired secretion of bile acids and organic anions, 7,8 although disruption of actin organization by itself does not seem to decrease canalicular secretion of bile salt and nonbile salt organic anions in isolated rat hepatocyte couplets.…”

Transport of organic anions in the liver. An update on bile acid, fatty acid, monocarboxylate, anionic amino acid, cholephilic organic anion, and anionic drug transport

“…Phalloidin was the first compound which was presumed to be a substrate of this transport system (Petzinger 1981). The topic of the liver organotropism of phalloidin due to its uptake by hepatic bile acid transporters has been reviewed (Petzinger 1984;Frimmer 1987;Petzinger et al 1987). In these studies the test bile acid was CA.…”

Alteration of axonal microfilaments alters Schwann cell lipid metabolism

“…To test the involvement of axonal microfilaments in intercellular communication, we examined the effect of microfilament perturbation on lipid metabolism of Schwann cells. Three toxins were used for this purpose: two of them (cytochalasin D and brevine) shorten actin filaments in vivo and increase gel fluidity in vitro (Bryan and Kurth, 1984;Bader et al, 1986) and the third (phalloidin) rigidifies microfilaments in vivo and decreases actin gel fluidity in vitro (Frimmer, 1987). Cytochalasin D was chosen because it is the only cytochalasin that does not interfere with glucose metabolism (Prentki et al, 1979).…”