In contrast to popular opinion phallotoxins do not play a role in
poisoning with Amanita phalloides when the fungi are ingested orally. All toxic properties of this mushroom are due to amatoxins which, in contrast to the phallotoxins, are absorbed upon ingestion. Nearly all experiments on intact animals were performed by parenteral injection of
phalloidin and therefore, most of these are unsuitable for practical consideration. In the present survey, however, a series of important findings are discussed, which provide insight into various functions of liver cells. When present in the blood,
phalloidin and other phallotoxins are selectively taken up by hepatocytes. No other types of cells are sensitive to the toxin. No extrahepatic tissue is primarily impaired by
phalloidin.
Phalloidin cannot be degraded by
peptidases or by
proteases occurring in animals.
Phalloidin is therefore a useful model substance for studies on the uptake of
cyclopeptides by liver cells. The carrier system responsible for the active uptake of
phalloidin can also translocate
antamanide and several cyclic modifications of
somatostatin. Phallotoxins bind with high affinity to microfilamentous structures, in particular to
F-actin [Govindan et al., Naturwissenschaften, 59 (1972) 521-522] whereas phallotoxins are not bound to the monomer (
G-actin). With respect to the strong organotropism of phallotoxins, intravenously injected
phalloidin binds preferentially to microfilamentous
F-actin of hepatocytes.
Phalloidin is therefore a tool for inactivation of microfilamentous functions specifically in liver cells, and is suitable as a prototype of a cholestatic agent. In perfused livers arrest of bile flow is the earliest effect seen after addition of the toxin. In cells from other tissues
phalloidin is only toxic when applied by intracellular microinjection.
Phalloidin poisoning has been often used as a model for liver damage in the testing of hepatoprotective drugs. This substance is, however, not useful for such studies since the mechanism of
phalloidin poisoning is too specific for interpretation in the sense of general liver protection.